COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

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.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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.

Cell replacement with stem cell-derived retinal ganglion cells from different protocols

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness worldwide.There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury.Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases.In this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes.Next,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and clusters.This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

Long-term outcome of stem cell transplantation with and without anti-tumor necrotic factor therapy in perianal fistula with Crohn’s disease

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.

Controversies regarding transplantation of mesenchymal stem cells

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.

Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation

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.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

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.

Stem cell transplantation for spinal cord injury： a meta-analysis of treatment effectiveness and safety

OBJECTIVE： The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury（SCI）.DATA SOURCES： PubM ed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and Sino Med databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016. DATA SELECTION： Randomized controlled trials comparing stem cell transplantation with rehabilitation treatment for patients with SCI. Inclusion criteria：（1） Patients with SCI diagnosed according to the American Spinal Injury Association（ASIA） International standards for neurological classification of SCI;（2） patients with SCI who received only stem cell transplantation therapy or stem cell transplantation combined with rehabilitation therapy;（3） one or more of the following outcomes reported： outcomes concerning neurological function including sensory function and locomotor function, activities of daily living, urination functions, and severity of SCI or adverse effects. Studies comprising patients with complications, without full-text, and preclinical animal models were excluded. Quality of the included studies was evaluated using the Cochrane risk of bias assessment tool and Rev Man V5.3 software, provided by the Cochrane Collaboration, was used to perform statistical analysis. OUTCOME MEASURES： ASIA motor score, ASIA light touch score, ASIA pinprick score, ASIA impairment scale grading improvement rate, activities of daily living score, residual urine volume, and adverse events.RESULTS： Ten studies comprising 377 patients were included in the analysis and the overall risk of bias was relatively low level. Four studies did not detail how random sequences were generated, two studies did not clearly state the blinding outcome assessment, two studies lacked blinding outcome assessment, one study lacked follow-up information, and four studies carried out selective reporting. Compared with rehabilitation therapy, stem cell transplantation significantly increased the lower limb light touch score（odds ratio（OR） = 3.43, 95% confidence interval（CI）： 0.01 – 6.86, P = 0.05）, lower limb pinprick score（OR = 3.93, 95%CI： 0.74 – 7.12, P = 0.02）, ASI grading rate（relative risk（RR） = 2.95, 95%CI： 1.64 – 5.29, P = 0.0003）, and notably reduced residual urine volume（OR = –8.10, 95%CI： –15.09 to –1.10, P = 0.02）. However, stem cell transplantation did not significantly improve motor score（OR = 1.89, 95%CI： –0.25 to 4.03, P = 0.08） or activities of daily living score（OR = 1.12, 95%CI： –1.17 to 4.04, P = 0.45）. Furthermore, stem cell transplantation caused a high rate of mild adverse effects（RR = 14.49, 95%CI： 5.34 – 34.08, P 〈 0.00001）; however, these were alleviated in a short time. CONCLUSION： Stem cell transplantation was determined to be an efficient and safe treatment for SCI and simultaneously improved sensory and bladder functions. Although associated minor and temporary adverse effects were observed with transplanted stem cells, spinal cord repair and axon remyelination were apparent. More randomized controlled trials with larger sample sizes and longer follow-up times are needed to further validate the effectiveness of stem cell transplantation in the treatment of SCI.

Focus on limbal stem cell deficiency and limbal cell transplantation

Limbal stem cell deficiency(LSCD)causes severe vision impairment and can lead to blindness,representing one of the most challenging ocular surface disorders.Stem cell deficiency can be congenital or,more often,acquired.The categorization of ocular surface transplantation techniques is crucial to achieving treatment homogeneity and quality of care,according to the anatomic source of the tissue being transplanted,genetic source,autologous or allogenic transplantation(to reflect histocompatibility in the latter group),and cell culture and tissue engineering techniques.The aim of this minireview is to provide a summary of the management of LSCD,from clinical characteristics and therapeutic outcomes to the development of novel therapeutic approaches.The manuscript also briefly summarizes recent findings in the current literature and outlines the future challenges to overcome in the management of the major types of ocular surface failure.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

Stem cell therapy in retinal diseases

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness.Despite intensive research in the field of retinal disorders,there is currently no curative treatment.Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development.In the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for transplantation.In the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies.In this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

Stem cell transplantation for treating stroke:status,trends and development

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The ma- jority of these articles were from the USA （854, 39.4%）, with the journal Stroke publishing the most articles （145, 6.7%）. Of the published articles, 143 were funded by the National Institutes of Health （accounting for 6.6% of total publications）, and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided finan- cial support （$130 million subsidy） for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA （ranked first place）. China had the maximum number of registered research or clinical trials （10 projects）.

Stem cell transplantation for treating spinal cord injury A literature comparison between studies of stem cells obtained from various sources

OBJECTIVE： To identify global research trends of stem cell transplantation for treating spinal cord injury using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating spinal cord injury from 2002 to 2011 using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on stem cell transplantation for treating spinal cord injury that were published and indexed in the Web of Science; （b） type of articles： original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） documents that were not published in the public domain; and （c） a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES： （1） Annual publication output; （2） distribution according to country; （3） distribution according to institution; （4） distribution according to journals; （5） distribution according to funding agencies; and （6） top cited articles over the last 10 years. RESULTS： Bone marrow mesenchymal stem cells and embryonic stem cells have been widely used for treating spinal cord injury. In total, 191 studies of bone marrow mesenchymal stem cell transplantation and 236 studies of embryonic stem cell transplantation for treating spinal cord injury appeared in the Web of Science from 2002 to 2011, and almost half of which were derived from American or Japanese authors and institutes. The number of studies of stem cell transplantation for treating spinal cord injury has gradually increased over the past 10 years. Most papers on stem cell transplantation for treating spinal cord injury appeared in journals with a particular focus on stem cell research, such as Stem Cells and Cell Transplantation. Although umbilical cord blood stem cells and adipose-derived stem cells have been studied for treating spinal cord injury, the number of published papers was much smaller, with only 21 and 17 records, respectively, in the Web of Science. CONCLUSION： Based on our analysis of the literature and research trends, we found that stem cells transplantation obtained from various sources have been studied for treating spinal cord injury; however, it is difficult for researchers to reach a consensus on this theme.

Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation

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.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma:A case report

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL), a unique subtype of peripheral Tcell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation(ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis(HLH) has a worse prognosis than B-cell lymphoma-triggered HLH.CASE SUMMARY We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL(Stage Ⅳ, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1;prednisone 100 mg on days 1-5;and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen(busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids.CONCLUSION It is possible that development of HLH is related to immune reconstitution after ASCT.

Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report

BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.

Ocular manifestations and quality of life in patients after hematopoietic stem cell transplantation

AIM:To explore the relationship between ocular and systemic conditions and the impact of ocular complications on the quality of life(QOL)in patients after allogeneic hematopoietic stem cell transplantation(ALLO-HSCT).METHODS:Forty-four patients with severe hematopoietic disease were enrolled after ALLO-HSCT at our center from July 2018 to October 2020.They completed two questionnaires:the Ocular Surface Disease Index(OSDI)and the quality-of-life scale for Chinese patients with visual impairment(SQOL-DV1).Ocular conditions and systemic conditions were also assessed.RESULTS:Eye damage was correlated with total bilirubin(P=0.005),and gamma-glutamyl transferase(GGT)(P=0.021).There was no significant correlation between the overall QOL score and OSDI(P=0.8226)or SQOLDV1(P=0.9526)scores.The OSDI and the overall QOL score were not correlated with ocular conditions,including best-corrected visual acuity(BCVA),intraocular pressure,Schirmer tear test II,sodium fluorescein staining,tear film breakup time,and tear meniscus height.SQOLDV1 was correlated with BCVA(P=0.0007),sodium fluorescein staining(P=0.007),and tear film breakup time(P=0.0146).CONCLUSION:In some patients,early ocular symptoms are not evident after ALLO-HSCT,while ocular surface complications can be observed after a comprehensive ophthalmological examination.Especially for those with elevated total bilirubin or GGT,regular ophthalmic follow-up visits are essential to diagnose and treat ocular graft versus host disease(o GVHD),especially for patients with elevated total bilirubin or GGT.

Haploidentical hematopoietic stem cell transplantation as promising therapy in the improved survival of pediatric patients with leukemias and myelodysplasias

BACKGROUND Haploidentical hematopoietic stem cell transplantation(Haplo-HSCT)is often performed in children with hematologic malignancies.Faced with the gap in the literature regarding the approach to experiences related to Haplo-HSCT with pediatric patients with leukemias and myelodysplasias aged up to 18 years,there was an interest in exploring the clinical outcomes of patients undergoing this treatment.AIM To identify and summarize the scientific contributions available on Haplo-HSCT performed in the last 10 years in children and adolescents with myeloid and lymphoid leukemias and myelodysplasias,aged up to 18 years.METHODS This is a descriptive systematic review.We extracted data including characteristics of participants,health condition,characteristics of the donation,conditioning regimen,recurrent clinical complications and clinical outcomes.The Virtual Health Library Brazil,PubMed,EMBASE,and SciELO platforms were used,finding a total of 1052 studies.After the eligibility criteria and complete reading of the texts,18 articles were included for analysis.RESULTS The total sample of all study cohorts was 1825 patients,mostly male,the highest reported median age was 15.0 years and the lowest was 1.2 years.Acute graftversus-host disease and chronic graft-versus-host disease were observed in almost all studies.Relapse,graft rejection and delayed immune recovery were identified as major clinical challenges.Pre-transplant minimal positive residual disease was identified in 288 patients.Infections are also among the main clinical complications,viral,bacterial and fungal infections being reported.It is observed that in the 5-year interval,the lowest rates of EFS and overall survival(OS)were 29.5%and 68.0%,respectively.While,the highest rates of EFS and OS,in the same interval,were 80.1%and 81.0%.CONCLUSION Haplo-HSCT represents a promising therapy,considering the potential number of possible donors and the conditioning and treatment platforms that can be offered.The results obtained show that this type of transplant has a strong antileukemic effect,with generally favorable OS rates.Overcoming relapse as the first cause of transplant failure is the great clinical challenge.

Allogeneic hematopoietic stem cell transplantation in a 3-year-old boy with congenital pyruvate kinase deficiency: A case report

BACKGROUND The understanding regarding genetic variation,pathophysiology,and complications associated with pyruvate kinase deficiency(PKD)in red blood cells has been explained largely,and supportive treatment is currently the main management strategy.Etiotropic managements,including transplantation and genome editing,supplying for substitute dugs of the pyruvate kinase,are all under research.CASE SUMMARY We herein report a 3-year-old boy with severe transfusion-dependent PKD cured by unrelated identical peripheral blood stem cell transplantation(PBSCT).Hemoglobin was corrected to a normal level by gene correction after PBSCT,with no complication related to the transplantation.CONCLUSION Hematopoietic stem cell transplantation could be a substitute for transfusiondependent PKD.

Adipose mesenchymal stem cell-derived extracellular vesicles reduce glutamate-induced excitotoxicity in the retina

Adipose mesenchymal stem cells(ADSCs)have protective effects against glutamate-induced excitotoxicity,but ADSCs are limited in use for treatment of optic nerve injury.Studies have shown that the extracellular vesicles(EVs)secreted by ADSCs(ADSC-EVs)not only have the function of ADSCs,but also have unique advantages including non-immunogenicity,low probability of abnormal growth,and easy access to target cells.In the present study,we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography.In addition,R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium,downregulation ofα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor(AMPAR)subunit GluA2,and phosphorylation of GluA2 and protein kinase C alpha in vitro.A protein kinase C alpha agonist,12-O-tetradecanoylphorbol 13-acetate,inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells.These findings suggest that ADSCEVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.