Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells a...Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.展开更多
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und...Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.展开更多
Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techni...Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.展开更多
BACKGROUND Cerebrovascular accident(CVA)is a major global contributor to death and disability.As part of its medical management,researchers have recognized the importance of promising neuroprotective strategies,where ...BACKGROUND Cerebrovascular accident(CVA)is a major global contributor to death and disability.As part of its medical management,researchers have recognized the importance of promising neuroprotective strategies,where stem cell transplantation(SCT)is thought to confer advantages via trophic and neuroprotective effects.AIM To evaluate the current state of research on SCT in patients with CVA,assess key trends and highlight literature gaps.METHODS PubMed was screened for SCT in CVA-related articles in October 2023,for each country during the period between 2000 and 2023.Using the World Bank data,total population and gross domestic product were collected for comparison.VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query.Graphs and tables were obtained using Microsoft Office Excel.RESULTS A total of 6923 studies were identified on SCT in CVA,making 0.03%of all published studies worldwide.Approximately,68%were conducted in high-income countries,with a significant focus on mesenchymal stem cells.The journal“Stroke”featured the largest share of these articles,with mesenchymal SCT having the highest rate of inclusion,followed by hematopoietic SCT.Over time,there has been a noticeable shift from in vitro studies,which assess stem cell proliferation and neurogenesis,to in vivo studies aimed at evaluating efficacy and safety.Additionally,the number of reviews increased along this approach.CONCLUSION This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity,and highlights both current trends and gaps.Having a potential therapeutic role in CVA,more research is needed in the future to focus on different aspects of SCT,aiming to reach a better treatment strategy and improve life quality in patients.展开更多
Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell su...Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell survival,demand extensive investigation.Disease-associated stress microenvironments further complicate outcomes.This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations.Additionally,questions arise about how to predict,track,and comprehend cell fate post-transplantation.In vivo cellular imaging has emerged as a critical requirement for both short-and long-term safety and efficacy studies.However,translating preclinical imaging methods to clinical settings remains challenging.The fate and function of transplanted cells within the host environment present intricate challenges,including MSC engraftment,variability,and inconsistencies between preclinical and clinical data.The study explored the impact of high glucose concentrations on MSC survival in diabetic environments,emphasizing mitochondrial factors.Preserving these factors may enhance MSC survival,suggesting potential strategies involving genetic modification,biomaterials,and nanoparticles.Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies.These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data,computational disease modeling,and possibly artificial intelligence to enable deterministic insights.展开更多
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration...Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.展开更多
Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematop...Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.展开更多
BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.H...BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.展开更多
BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most ...BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.Th...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.展开更多
Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intric...Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.展开更多
BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmu...BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.展开更多
Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out fro...Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out from the waitlist.Recently,immunotherapy has shown great promise in the treatment of advanced HCC.However,the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection.One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host.Besides,the safety,availability,and costs of immunotherapy are other challenges that need to be addressed.Here,we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis.Statistically,the incidence of rejection was 25.0%pre-transplant and 18.5%post-transplant.Based on the review of these clinical studies,we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence.To date,the clinical experience on the use of immunotherapy before or after LT comes from individual case studies.Although some of the reported results are promising,they are not sufficient to support the standardized use of immunotherapy in clinical practice.展开更多
Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endot...Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.展开更多
As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements...As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.展开更多
New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Defici...New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses.展开更多
BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff...BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.展开更多
Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cel...Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.展开更多
Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, al...Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, alloimmunization, and transfusion reactions. These risks have sparked an ongoing debate regarding the overall impact of transfusions on patient outcomes. Thus, this study aimed to evaluate the impact of Red Blood Cells (RBCs) and/or platelet transfusion on the infection incidence and overall survival in AHSCT patients. Methods: We performed a retrospective analysis of clinical and laboratory data of sixty adult patients with primary malignant hematological disorder who had undergone AHSCT. Participants’ data were categorized into two groups;Group 1 (low transfusion group) consisted of patients receiving 10 units. Quantitative data were expressed as mean ± SD. The t-test of significance and Chi-square (χ2) test were used, with p ≤ 0.05 considered significant. Result: A total of 60 patients’ data was included. In Group 1, out of 30 patients, 13 (43.33%) developed infections. In contrast, Group 2 had 21 (70%) out of 30 patients develop infections. Group 1 had a higher survival rate (57.8%) than Group 2 (transfusion > 10 units) (46.2%) with a chi-square value = 23.56, and p-value Conclusion: The volume of blood product transfusions has a considerable impact on patient outcomes, particularly infection and survival rates. Additional long-term prospective studies and larger randomized controlled trials are needed to strengthen the evidence for determining transfusion protocols for these patients.展开更多
Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recogn...Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.展开更多
基金supported by the Stem Cell and Translation National Key Project,No.2016YFA0101403(to ZC)the National Natural Science Foundation of China,Nos.82171250 and 81973351(to ZC)+6 种基金the Natural Science Foundation of Beijing,No.5142005(to ZC)Beijing Talents Foundation,No.2017000021223TD03(to ZC)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan,No.CIT&TCD20180333(to ZC)Beijing Municipal Health Commission Fund,No.PXM2020_026283_000005(to ZC)Beijing One Hundred,Thousand,and Ten Thousand Talents Fund,No.2018A03(to ZC)the Royal Society-Newton Advanced Fellowship,No.NA150482(to ZC)the National Natural Science Foundation of China for Young Scientists,No.31900740(to SL)。
文摘Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.
基金Supported by the National Natural Science Foundation of China,No.82000586 and No.82241221and Shanghai Immune Therapy Institute.
文摘Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.
文摘BACKGROUND Cerebrovascular accident(CVA)is a major global contributor to death and disability.As part of its medical management,researchers have recognized the importance of promising neuroprotective strategies,where stem cell transplantation(SCT)is thought to confer advantages via trophic and neuroprotective effects.AIM To evaluate the current state of research on SCT in patients with CVA,assess key trends and highlight literature gaps.METHODS PubMed was screened for SCT in CVA-related articles in October 2023,for each country during the period between 2000 and 2023.Using the World Bank data,total population and gross domestic product were collected for comparison.VOSviewer_1.6.19 was used to create the VOS figure using the results of the same query.Graphs and tables were obtained using Microsoft Office Excel.RESULTS A total of 6923 studies were identified on SCT in CVA,making 0.03%of all published studies worldwide.Approximately,68%were conducted in high-income countries,with a significant focus on mesenchymal stem cells.The journal“Stroke”featured the largest share of these articles,with mesenchymal SCT having the highest rate of inclusion,followed by hematopoietic SCT.Over time,there has been a noticeable shift from in vitro studies,which assess stem cell proliferation and neurogenesis,to in vivo studies aimed at evaluating efficacy and safety.Additionally,the number of reviews increased along this approach.CONCLUSION This bibliometric analysis provides a comprehensive guide for physicians and researchers in the field through an objective overview of research activity,and highlights both current trends and gaps.Having a potential therapeutic role in CVA,more research is needed in the future to focus on different aspects of SCT,aiming to reach a better treatment strategy and improve life quality in patients.
基金Supported by the Romanian Ministry of Research,Innovation and Digitization,CNCS/CCCDI-UEFISCDI,project number ERANETEURONANOMED-3-OASIs,within PNCDI III(contract number 273/2022).
文摘Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell survival,demand extensive investigation.Disease-associated stress microenvironments further complicate outcomes.This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations.Additionally,questions arise about how to predict,track,and comprehend cell fate post-transplantation.In vivo cellular imaging has emerged as a critical requirement for both short-and long-term safety and efficacy studies.However,translating preclinical imaging methods to clinical settings remains challenging.The fate and function of transplanted cells within the host environment present intricate challenges,including MSC engraftment,variability,and inconsistencies between preclinical and clinical data.The study explored the impact of high glucose concentrations on MSC survival in diabetic environments,emphasizing mitochondrial factors.Preserving these factors may enhance MSC survival,suggesting potential strategies involving genetic modification,biomaterials,and nanoparticles.Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies.These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data,computational disease modeling,and possibly artificial intelligence to enable deterministic insights.
基金supported in part by NIH R01 NS100531,R01 NS103481NIH R21NS130241(to LD)+3 种基金Merit Review Award I01 BX002356,I01 BX003705 from the U.S.Department of Veterans AffairsIndiana Spinal Cord and Brain Injury Research Foundation(No.19919)Mari Hulman George Endowment Funds(to XMX)Indiana Spinal Cord&Brain Injury Research Fund from ISDH(to NKL and LD)。
文摘Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
基金supported by the Key Program of the National Natural Science Foundation of China(No.81930004)the National Natural Science Foundation of China(No.82170208)+2 种基金Tongzhou District Distinguished Young Scholars(No.JCQN2023009)Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)Beijing Natural Science Foundation(No.Z230016)。
文摘Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.
基金Supported by the grants from the Asan Institute for Life Sciences,Asan Medical Center,Seoul,Korea,No.2019IF0593 and No.2020IP0039.
文摘BACKGROUND Stem cell transplantation is a promising therapeutic option for curing perianal fistula in Crohn’s disease(CD).Anti-tumor necrotic factor(TNF)therapy combined with drainage procedure is effective as well.However,previous studies are limited to proving whether the combination treatment of biologics and stem cell transplantation improves the effect of fistula closure.AIM This study aimed to evaluate the long-term outcomes of stem cell transplantation and compare Crohn’s perianal fistula(CPF)closure rates after stem cell transplantation with and without anti-TNF therapy,and to identify the factors affecting CPF closure and recurrence.METHODS The patients with CD who underwent stem cell transplantation for treating perianal fistula in our institution between Jun 2014 and December 2022 were enrolled.Clinical data were compared according to anti-TNF therapy and CPF closure.RESULTS A total of 65 patients were included.The median age of females was 26 years(range:21-31)and that of males was 29(44.6%).The mean follow-up duration was 65.88±32.65 months,and complete closure was observed in 50(76.9%)patients.The closure rates were similar after stem cell transplantation with and without anti-TNF therapy(66.7%vs 81.6%at 3 year,P=0.098).The patients with fistula closure had short fistulous tract and infrequent proctitis and anorectal stricture(P=0.027,0.002,and 0.008,respectively).Clinical factors such as complexity,number of fistulas,presence of concurrent abscess,and medication were not significant for closure.The cumulative 1-,2-,and 3-year closure rates were 66.2%,73.8%,and 75.4%,respectively.CONCLUSION Anti-TNF therapy does not increase CPF closure rates in patients with stem cell transplantation.However,both refractory and non-refractory CPF have similar closure rates after additional anti-TNF therapy.Fistulous tract length,proctitis,and anal stricture are risk factors for non-closure in patients with CPF after stem cell transplantation.
基金Supported by National Natural Science Foundation of China,No.82270649.
文摘BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.
基金Supported by The National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008-C01.
文摘Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.
文摘BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.
基金supported by grants from National Key Research and Development Program of China(No.2021YFA1100500)the Major Research Plan of the National Natural Science Foundation of China(No.92159202)+3 种基金Key Program,National Natural Science Foundation of China(No.81930016)Key Research&Development Plan of Zhejiang Province(No.2019C0350)Key Research&Development Program of Zhejiang Province(No.2022C03108)Young Program of National Natural Science Funds(No.81802889).
文摘Liver transplantation(LT)is a highly curative therapy for patients with hepatocellular carcinoma(HCC).However,due to the shortage of donor livers and rapid progression of HCC,a majority of patients are dropped out from the waitlist.Recently,immunotherapy has shown great promise in the treatment of advanced HCC.However,the use of immunotherapy is limited in LT mainly due to the potentially increasing risk of graft rejection.One of the main challenges for researchers is the protection of donor graft from an immunotherapy-boosted immune response mounted by the host.Besides,the safety,availability,and costs of immunotherapy are other challenges that need to be addressed.Here,we reviewed the literature involving patients who received immunotherapy prior to transplant to avoid waitlist dropouts and following transplantation to prevent the progression of tumor recurrence and metastasis.Statistically,the incidence of rejection was 25.0%pre-transplant and 18.5%post-transplant.Based on the review of these clinical studies,we can conclude that conducting clinical trials on the safety and efficacy of currently available immunotherapy drugs and identifying novel immunotherapy targets through extensive research may be promising for patients who do not meet the selection criteria for LT and who experience post-transplant recurrence.To date,the clinical experience on the use of immunotherapy before or after LT comes from individual case studies.Although some of the reported results are promising,they are not sufficient to support the standardized use of immunotherapy in clinical practice.
基金supported by Key Research and Development Plan of Xuzhou Science and Technology Bureau,No.KC21162(to XMZ)a grant from Jiangsu Key Laboratory of Brain Disease Bioinformationg,No.XZSYSKF2021018(to XMZ)+1 种基金Natural Science Fund for Colleges and Universities in Jiangsu Province,No.19KJB320024(to HNY)the Science and Technology Development Fund from Affiliated Hospital of Xuzhou Medical University,Nos.XYFM2021024(to XMZ),XYFM2021006(to DH).
文摘Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.
基金Supported by the Scientific Research Project of the Sichuan Province Education Department,No. 16ZA0241the National Natural Science Foundation of China,No. 82060268the Guangxi Natural Science Foundation of China,No. 2020JJA140124。
文摘As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
文摘New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells.Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells.Thus,the disruption of photoreceptors takes place.However,even in advanced forms of retinal degeneration,a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact.This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region.The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities.The eyeball's immunological privilege,characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues,is responsible for the low rate of graft rejection in transplant patients.The main discoveries highlight the capacity of embryonic stem cells(ESCs)and induced pluripotent stem cells to regenerate damaged retinal regions.Recent progress has shown significant enhancements in transplant procedures and results.The research also explores the ethical ramifications linked to the utilization of stem cells,emphasizing the ongoing issue surrounding ESCs.The analysis centers on recent breakthroughs,including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation.Moreover,researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation.The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location.Currently,most therapy approaches are in the first phases of development and necessitate further research,including both pre-clinical and clinical trials,to attain favorable visual results for individuals suffering from retinal degenerative illnesses.
基金Supported by the Hospital Research Fund,No.SDFEYBS1805,No.SDFEYGJ2013 and No.XKTJ-HRC20210015Suzhou Science and Technology Development Project,No.SYS2020105,No.SKJY2021078 and No.2022SS43+2 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLZD2021002CNNC Elite Talent Program2022 State Key Laboratory of Radiological Medicine and Radiation Protection jointly built by Province and Ministry,No.GZK1202244.
文摘BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.
基金supported by Grant National Key R&D Program of China (No.2020YFC2005600 and No.2020YFC2005605)。
文摘Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.
文摘Background: While blood product transfusion is essential for managing hematologic deficits in Allogenic Hematopoietic stem cell transplant (AHSCT) recipients, it has risks including infectious disease transmission, alloimmunization, and transfusion reactions. These risks have sparked an ongoing debate regarding the overall impact of transfusions on patient outcomes. Thus, this study aimed to evaluate the impact of Red Blood Cells (RBCs) and/or platelet transfusion on the infection incidence and overall survival in AHSCT patients. Methods: We performed a retrospective analysis of clinical and laboratory data of sixty adult patients with primary malignant hematological disorder who had undergone AHSCT. Participants’ data were categorized into two groups;Group 1 (low transfusion group) consisted of patients receiving 10 units. Quantitative data were expressed as mean ± SD. The t-test of significance and Chi-square (χ2) test were used, with p ≤ 0.05 considered significant. Result: A total of 60 patients’ data was included. In Group 1, out of 30 patients, 13 (43.33%) developed infections. In contrast, Group 2 had 21 (70%) out of 30 patients develop infections. Group 1 had a higher survival rate (57.8%) than Group 2 (transfusion > 10 units) (46.2%) with a chi-square value = 23.56, and p-value Conclusion: The volume of blood product transfusions has a considerable impact on patient outcomes, particularly infection and survival rates. Additional long-term prospective studies and larger randomized controlled trials are needed to strengthen the evidence for determining transfusion protocols for these patients.
文摘Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.