In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for es...In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix(ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection(EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.展开更多
Bone regeneration is a multifaceted process involving the well-coordinated interaction of cellular functions such as the regulation of inflammation,the for-mation of new blood vessels,and the development of bone tissu...Bone regeneration is a multifaceted process involving the well-coordinated interaction of cellular functions such as the regulation of inflammation,the for-mation of new blood vessels,and the development of bone tissue.Bone rege-neration is a multifaceted process involving the well-coordinated interplay of multiple cellular activities,such as inflammation control,blood vessel and bone tissue.Zhang et al developed a multifunctional hydrogel system embedded with bone marrow stromal cell-derived exosomes to address the challenges of large bone defects.This innovative approach demonstrated the dual-role capability of bone marrow stromal cell-derived exosomes in directing cell fate by significantly enhancing both angiogenesis and osteogenic differentiation in vitro.The hydrogel system effectively promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype,fostering an environment that supports bone repair.The effectiveness of this hydrogel was validated in a murine fracture model,which promoted significant bone regeneration and functional vascularization.Despite compelling evidence,this study highlights areas for further investigation,including detailed descriptions of experimental procedures,control group selection,long-term outcomes,and the evaluation of inflammation status in vivo.Addressing these limitations will enhance the robustness and impact of the findings.展开更多
Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about...Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenos...A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement.Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus.Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease,important barriers remain that need to be addressed.展开更多
The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that tr...The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.展开更多
PLLA-magnesium composites have been widely investigated as potential biodegradable materials for bone implants.Lower/higher corrosion resistance of the crystalized/amorphous magnesium alloys allows tailoring of biodeg...PLLA-magnesium composites have been widely investigated as potential biodegradable materials for bone implants.Lower/higher corrosion resistance of the crystalized/amorphous magnesium alloys allows tailoring of biodegradability rate.In this work,the amorphous Mg_(65)Zn_(30)Ca_(5)was investigated versus traditional crystalized Mg_(65)Zn_(30)Ca_(5),and a PLLA-Mg_(65)Zn_(30)Ca_(5)composite has been successfully fabricated using hot injection process.Furthermore,the high corrosion resistance of the amorphous Mg_(65)Zn_(30)Ca_(5)prevented the high alkalization and deterioration of mechanical strength.In addition,the high Zn content intended to improve the glass forming ability,also enhances the anti-bacterial property of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite.The remarkable performance of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite shows its promising application in bone repair and tissue regeneration.展开更多
The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's disease.Therefore,competent ther...The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's disease.Therefore,competent therapies that could improve the healthspan of people have great significance.Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age.Metformin,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive dysfunction.However,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies.While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still unclear.Moreover,a previous animal model study implied that metformin could adversely affect cognitive function in the aged.However,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age.The study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the hippocampus.The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function.Nonetheless,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.展开更多
Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input...Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life(Kupers and Ptito,2014).More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.展开更多
It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after transplantation.Adenosine is a purine nucleoside that has the function to suppress...It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after transplantation.Adenosine is a purine nucleoside that has the function to suppress cellular metabolism and has been previously proposed as a method to prolong cell viability under hypoxia.In this study,we optimized the dose concentration of adenosine for incorporation into bioprinted constructs to preserve long-term cell viability in vitro.Our results showed that muscle cells(C2C12)containing 6,7,or 8 mM adenosine maintained high cell viability for 20 days under hypoxic conditions(0.1%O2),whereas cells without adenosine treatment showed 100%cell death after 11 days.After 20 days under hypoxic conditions,muscle cells treated with adenosine proliferated and differentiated when transferred to normoxic conditions.From these adenosine concentrations,6 mM was picked as the optimized adenosine concentration for further investigations due to its most effective results on improving cell viability.The bioprinted muscle constructs containing adenosine(6 mM)maintained high cell viability for 11 days under hypoxic conditions,while the control constructs without adenosine had no live cells.For in vivo validation,the bioprinted constructs with adenosine implanted under the dorsal subcutaneous space in mice,showed the enhanced formation of muscle tissue with minimal central necrosis and apoptosis,when compared to the constructs without adenosine.These positive in vitro and in vivo results demonstrate that the use of adenosine is an effective approach to preventing the challenge of hypoxia-induced necrosis in bioprinted tissues for clinical translation.展开更多
The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engin...The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation.Specifically,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in vivo.Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process.The present review provides a brief overview of bioreactor engineering considerations.In addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.展开更多
Engineered functional organs or tissues,created with autologous somatic cells and seeded on biodegradable or hydrogel scaffolds,have been developed for use in individualswith tissue damage suffered fromcongenital diso...Engineered functional organs or tissues,created with autologous somatic cells and seeded on biodegradable or hydrogel scaffolds,have been developed for use in individualswith tissue damage suffered fromcongenital disorders,infection,irradiation,or cancer.However,in those patients,abnormal cells obtained by biopsy fromthe compromised tissue could potentially contaminate the engineered tissues.Thus,an alternative cell source for construction of the neo-organ or functional recovery of the injured or diseased tissues would be useful.Recently,we have found stem cells existing in the urine.These cells are highly expandable,and have self-renewal capacity,paracrine properties,and multi-differentiation potential.As a novel cell source,urine-derived stem cells(USCs)provide advantages for cell therapy and tissue engineering applications in regeneration of various tissues,particularly in the genitourinary tract,because they originate from the urinary tract system.Importantly,USCs can be obtained via a non-invasive,simple,and low-cost approach and induced with high efficiency to differentiate into three dermal cell lineages.展开更多
Objective This study aims to explore the complex relationship between social engagement and depressive symptoms among older adults in China,focusing particularly on the moderating role of marital status.Methods This s...Objective This study aims to explore the complex relationship between social engagement and depressive symptoms among older adults in China,focusing particularly on the moderating role of marital status.Methods This study used data from the latest Chinese Longitudinal Healthy Longevity Survey(CLHLS).The analysis used the latent class analysis to delineate personality clusters and hierarchical linear regression,supplemented by the PROCESS macro,to investigate the effects of social engagement and marital status on depressive symptoms.Results The analysis encompassed 7,789 respondents(mean age:82.53[s=11.20]years),with 54%female.The personality analysis categorized participants into four clusters,with the majority(77.60%)classified as Confident Idealists,who exhibited the lowest levels of depressive symptoms.Hierarchical linear regression analysis yielded several significant findings:Higher levels of social engagement were significantly associated with fewer depressive symptoms(t=-7.932,P<0.001,B=-0.463).Marital status was a significant factor;married individuals reported fewer depressive symptoms compared to their unmarried counterparts(t=-6.368,P<0.001,B=-0.750).There was a significant moderating effect of marital status on the relationship between social engagement and depressive symptoms(t=-2.092,P=0.037,B=-0.217).Conclusion This study demonstrates that,among Chinese older adults,both social engagement and marital status significantly influence depressive symptoms.Higher social engagement,particularly in other activities like doing household chores,gardening,reading newspapers or books,and playing cards or Mahjong,is associated with fewer depressive symptoms,especially among married individuals.展开更多
Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseas...Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.展开更多
This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience ...This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience of higher-passage MSCs under stress conditions,challenging the common use of lower passage MSCs in clinical settings.While this study offers valuable perspectives on the adaptability of MSCs,it relies mainly on in vitro results from a single cell line,limiting broader applicability.It highlights the need for more comprehensive in vivo studies to validate these findings and better understand MSC behavior in clinical scenarios.展开更多
Neurite outgrowth inhibitor A(Nogo-A)is a major player in neural development and regeneration and the target of clinical trials aiming at promoting the regeneration of the central nervous system upon traumatic and isc...Neurite outgrowth inhibitor A(Nogo-A)is a major player in neural development and regeneration and the target of clinical trials aiming at promoting the regeneration of the central nervous system upon traumatic and ischemic injury.In this work,we investigated the functions of Nogo-A during tooth development to determine its role in dental physiology and pathology.Using immunohistochemistry and in situ hybridization techniques,we showed that Nogo-A is highly expressed in the developing mouse teeth and,most specifically,in the ameloblasts that are responsible for the formation of enamel.Using both Nogo-A knockout and K14-Cre;Nogo-A fl/fltransgenic mice,we showed that Nogo-A deletion in the dental epithelium leads to the formation of defective enamel.This phenotype is associated with overexpression of a set of specific genes involved in ameloblast differentiation and enamel matrix production,such as amelogenin,ameloblastin and enamelin.By characterising the interactome of Nogo-A in the dental epithelium of wild-type and mutant animals,we found that Nogo-A directly interacts with molecules important for regulating gene expression,and its deletion disturbs their cellular localisation.Furthermore,we demonstrated that inhibition of the intracellular,but not cell-surface,Nogo-A is responsible for gene expression modulation in ameloblasts.Taken together,these results reveal an unexpected function for Nogo-A in tooth enamel formation by regulating gene expression and cytodifferentiation events.展开更多
Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate i...Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs dam-aged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.展开更多
BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with cr...BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.展开更多
基金Supported by Award Number T32EBO01026-08,from the National Institute of Biomedical Imaging and Bioengineering, in part
文摘In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix(ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection(EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.
基金Supported by the National Natural Science Foundation of China,No.81500207the Pyramid Talent Project,China,No.YQ677.
文摘Bone regeneration is a multifaceted process involving the well-coordinated interaction of cellular functions such as the regulation of inflammation,the for-mation of new blood vessels,and the development of bone tissue.Bone rege-neration is a multifaceted process involving the well-coordinated interplay of multiple cellular activities,such as inflammation control,blood vessel and bone tissue.Zhang et al developed a multifunctional hydrogel system embedded with bone marrow stromal cell-derived exosomes to address the challenges of large bone defects.This innovative approach demonstrated the dual-role capability of bone marrow stromal cell-derived exosomes in directing cell fate by significantly enhancing both angiogenesis and osteogenic differentiation in vitro.The hydrogel system effectively promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype,fostering an environment that supports bone repair.The effectiveness of this hydrogel was validated in a murine fracture model,which promoted significant bone regeneration and functional vascularization.Despite compelling evidence,this study highlights areas for further investigation,including detailed descriptions of experimental procedures,control group selection,long-term outcomes,and the evaluation of inflammation status in vivo.Addressing these limitations will enhance the robustness and impact of the findings.
文摘Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
文摘A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement.Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus.Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease,important barriers remain that need to be addressed.
基金Supported by NIH Research Grants R01DK071614,1RC1DK 087151,and U01 DK073975-01
文摘The digestive tract is designed for the optimal processing of food that nourishes all organ systems.The esophagus,stomach,small bowel,and colon are sophisticated neuromuscular tubes with specialized sphincters that transport ingested food-stuffs from one region to another.Peristaltic contractions move ingested solids and liquids from the esophagus into the stomach;the stomach mixes the ingested nutrients into chyme and empties chyme from the stomach into the duodenum.The to-and-fro movement of the small bowel maximizes absorption of fat,protein,and carbohydrates.Peristaltic contractions are necessary for colon function and defecation.
基金supported by National Natural Science Foundation of China(Grant No.51471120)
文摘PLLA-magnesium composites have been widely investigated as potential biodegradable materials for bone implants.Lower/higher corrosion resistance of the crystalized/amorphous magnesium alloys allows tailoring of biodegradability rate.In this work,the amorphous Mg_(65)Zn_(30)Ca_(5)was investigated versus traditional crystalized Mg_(65)Zn_(30)Ca_(5),and a PLLA-Mg_(65)Zn_(30)Ca_(5)composite has been successfully fabricated using hot injection process.Furthermore,the high corrosion resistance of the amorphous Mg_(65)Zn_(30)Ca_(5)prevented the high alkalization and deterioration of mechanical strength.In addition,the high Zn content intended to improve the glass forming ability,also enhances the anti-bacterial property of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite.The remarkable performance of the PLLA-Mg_(65)Zn_(30)Ca_(5)composite shows its promising application in bone repair and tissue regeneration.
基金supported by grants from the National Institutes of Health (No.1R01NS106907,to AKS)the Department of Defense (Nos.W81XWH-17-1-0447 and W81XWH-19-1-0548,to AKS)。
文摘The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's disease.Therefore,competent therapies that could improve the healthspan of people have great significance.Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age.Metformin,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive dysfunction.However,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies.While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still unclear.Moreover,a previous animal model study implied that metformin could adversely affect cognitive function in the aged.However,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age.The study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the hippocampus.The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function.Nonetheless,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.
基金supported by National Institutes of Health Contracts P30-EY008098 and T32-EY017271-06(BethesdaMD)+14 种基金United States Department of Defense DM090217(ArlingtonVA)Alcon Research Institute Young Investigator Grant(Fort WorthTX)Eye and Ear Foundation(PittsburghPA)Research to Prevent Blindness(New YorkNY)Aging Institute Pilot Seed GrantUniversity of Pittsburgh(PittsburghPA)Postdoctoral Fellowship Program in Ocular Tissue Engineering and Regenerative OphthalmologyLouis J.Fox Center for Vision RestorationUniversity of Pittsburgh and UPMC(PittsburghPA)
文摘Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life(Kupers and Ptito,2014).More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.
文摘It is crucial to maintaining the viability of biofabricated human-sized tissues to ensure their successful survival and function after transplantation.Adenosine is a purine nucleoside that has the function to suppress cellular metabolism and has been previously proposed as a method to prolong cell viability under hypoxia.In this study,we optimized the dose concentration of adenosine for incorporation into bioprinted constructs to preserve long-term cell viability in vitro.Our results showed that muscle cells(C2C12)containing 6,7,or 8 mM adenosine maintained high cell viability for 20 days under hypoxic conditions(0.1%O2),whereas cells without adenosine treatment showed 100%cell death after 11 days.After 20 days under hypoxic conditions,muscle cells treated with adenosine proliferated and differentiated when transferred to normoxic conditions.From these adenosine concentrations,6 mM was picked as the optimized adenosine concentration for further investigations due to its most effective results on improving cell viability.The bioprinted muscle constructs containing adenosine(6 mM)maintained high cell viability for 11 days under hypoxic conditions,while the control constructs without adenosine had no live cells.For in vivo validation,the bioprinted constructs with adenosine implanted under the dorsal subcutaneous space in mice,showed the enhanced formation of muscle tissue with minimal central necrosis and apoptosis,when compared to the constructs without adenosine.These positive in vitro and in vivo results demonstrate that the use of adenosine is an effective approach to preventing the challenge of hypoxia-induced necrosis in bioprinted tissues for clinical translation.
基金US Army Medical Research and Development Command through the Medical Technology Enterprise Consortium under Contract#W81XWH-15-9-0001.
文摘The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore,maintain or improve tissue function following disease or injury.To maximize the biological function of a tissue-engineered clinical product,specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation.Specifically,the bioreactor should be designed to mimic the mechanical,electrochemical and biochemical environment that the product will be exposed to in vivo.Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process.The present review provides a brief overview of bioreactor engineering considerations.In addition,strategies for bioreactor automation,in-line product monitoring and quality assurance are discussed.
基金The authors acknowledge funding support from NIH grant U01CA166886(X.Zhou)National Natural Science Foundation of China(No.81100415)and(No.81371704)+1 种基金Chongqing Natural Science Foundation of Committee of Science and Technology(No.CSTC,2010BB5377)Doctoral Program of the Ministry of Education(No.20115503120009).
文摘Engineered functional organs or tissues,created with autologous somatic cells and seeded on biodegradable or hydrogel scaffolds,have been developed for use in individualswith tissue damage suffered fromcongenital disorders,infection,irradiation,or cancer.However,in those patients,abnormal cells obtained by biopsy fromthe compromised tissue could potentially contaminate the engineered tissues.Thus,an alternative cell source for construction of the neo-organ or functional recovery of the injured or diseased tissues would be useful.Recently,we have found stem cells existing in the urine.These cells are highly expandable,and have self-renewal capacity,paracrine properties,and multi-differentiation potential.As a novel cell source,urine-derived stem cells(USCs)provide advantages for cell therapy and tissue engineering applications in regeneration of various tissues,particularly in the genitourinary tract,because they originate from the urinary tract system.Importantly,USCs can be obtained via a non-invasive,simple,and low-cost approach and induced with high efficiency to differentiate into three dermal cell lineages.
基金supported by National Natural Science Foundation of China[72174183].
文摘Objective This study aims to explore the complex relationship between social engagement and depressive symptoms among older adults in China,focusing particularly on the moderating role of marital status.Methods This study used data from the latest Chinese Longitudinal Healthy Longevity Survey(CLHLS).The analysis used the latent class analysis to delineate personality clusters and hierarchical linear regression,supplemented by the PROCESS macro,to investigate the effects of social engagement and marital status on depressive symptoms.Results The analysis encompassed 7,789 respondents(mean age:82.53[s=11.20]years),with 54%female.The personality analysis categorized participants into four clusters,with the majority(77.60%)classified as Confident Idealists,who exhibited the lowest levels of depressive symptoms.Hierarchical linear regression analysis yielded several significant findings:Higher levels of social engagement were significantly associated with fewer depressive symptoms(t=-7.932,P<0.001,B=-0.463).Marital status was a significant factor;married individuals reported fewer depressive symptoms compared to their unmarried counterparts(t=-6.368,P<0.001,B=-0.750).There was a significant moderating effect of marital status on the relationship between social engagement and depressive symptoms(t=-2.092,P=0.037,B=-0.217).Conclusion This study demonstrates that,among Chinese older adults,both social engagement and marital status significantly influence depressive symptoms.Higher social engagement,particularly in other activities like doing household chores,gardening,reading newspapers or books,and playing cards or Mahjong,is associated with fewer depressive symptoms,especially among married individuals.
基金RN received funding from Swiss Centre for Applied Human ToxicologyHelmut Hortun Stiftung。
文摘Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.
基金Supported by the National Natural Science Foundation of China,No.81500207 to Xiao-Ting Liangand the Pyramid Talent Project,No.YQ677 to Yue Ding.
文摘This article discussed a study by Almahasneh et al,which investigated how high glucose and severe hypoxia affected mesenchymal stem cells(MSCs)at different passages.This research provides insights into the resilience of higher-passage MSCs under stress conditions,challenging the common use of lower passage MSCs in clinical settings.While this study offers valuable perspectives on the adaptability of MSCs,it relies mainly on in vitro results from a single cell line,limiting broader applicability.It highlights the need for more comprehensive in vivo studies to validate these findings and better understand MSC behavior in clinical scenarios.
基金supported by institutional funds from the University of Zurich(T.A.M)and from the Knut and Alice Wallenberg Foundation(C.C.)by additional competitive funds from the Swiss National Science Foundation(SNSF+2 种基金research grant 31003A_179389)(T.A.M.)from the Swiss Dental Association(SSOresearch grant 313-19)(T.A.M.,P.P.)。
文摘Neurite outgrowth inhibitor A(Nogo-A)is a major player in neural development and regeneration and the target of clinical trials aiming at promoting the regeneration of the central nervous system upon traumatic and ischemic injury.In this work,we investigated the functions of Nogo-A during tooth development to determine its role in dental physiology and pathology.Using immunohistochemistry and in situ hybridization techniques,we showed that Nogo-A is highly expressed in the developing mouse teeth and,most specifically,in the ameloblasts that are responsible for the formation of enamel.Using both Nogo-A knockout and K14-Cre;Nogo-A fl/fltransgenic mice,we showed that Nogo-A deletion in the dental epithelium leads to the formation of defective enamel.This phenotype is associated with overexpression of a set of specific genes involved in ameloblast differentiation and enamel matrix production,such as amelogenin,ameloblastin and enamelin.By characterising the interactome of Nogo-A in the dental epithelium of wild-type and mutant animals,we found that Nogo-A directly interacts with molecules important for regulating gene expression,and its deletion disturbs their cellular localisation.Furthermore,we demonstrated that inhibition of the intracellular,but not cell-surface,Nogo-A is responsible for gene expression modulation in ameloblasts.Taken together,these results reveal an unexpected function for Nogo-A in tooth enamel formation by regulating gene expression and cytodifferentiation events.
文摘Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs dam-aged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.
文摘BACKGROUND Immunosuppression has undoubtedly raised the overall positive outcomes in the post-operative management of solid organ transplantation. However, long-term exposure to immunosuppression is associated with critical systemic morbidities. De novo malignancies following orthotopic liver transplants (OLTs) are a serious threat in pediatric and adult transplant individuals. Data from different experiences were reported and compared to assess the connection between immunosuppression and de novo malignancies in liver transplant patients. AIM To study the role of immunosuppression on the incidence of de novo malignancies in liver transplant recipients. METHODS A systematic literature examination about de novo malignancies and immunosuppression weaning in adult and pediatric OLT recipients was described in the present review. Worldwide data were collected from highly qualified institutions performing OLTs. Patient follow-up, immunosuppression discontinuation and incidence of de novo malignancies were reported. Likewise, the review assesses the differences in adult and pediatric recipients by describing the adopted immunosuppression regimens and the different type of diagnosed solid and blood malignancy.RESULTS Emerging evidence suggests that the liver is an immunologically privileged organ able to support immunosuppression discontinuation in carefully selected recipients. Malignancies are often detected in liver transplant patients undergoing daily immunosuppression regimens. Post-transplant lymphoproliferative diseases and skin tumors are the most detected de novo malignancies in the pediatric and adult OLT population, respectively. To date, immunosuppression withdrawal has been achieved in up to 40% and 60% of well-selected adult and pediatric recipients, respectively. In both populations, a clear benefit of immunosuppression weaning protocols on de novo malignancies is difficult to ascertain because data have not been specified in most of the clinical experiences. CONCLUSION The selected populations of tolerant pediatric and adult liver transplant recipients greatly benefit from immunosuppression weaning. There is still no strong clinical evidence on the usefulness of immunosuppression withdrawal in OLT recipients on malignancies. An interesting focus is represented by the complete reconstitution of the immunological pathways that could help in decreasing the incidence of de novo malignancies and may also help in treating liver transplant patients suffering from cancer.