stem cells

摘要： 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.

摘要： Numerous studies have shown that keratin 6B(KRT6B)is involved in the production and progression of tumors,and is closely related to the prognosis of tumors.OBJECTIVE:To observe the expression of keratin 6B in CD44^(+)bladder cancer stem cells and to show the influence of keratin 6B on proliferation,migration,and self-renewal of bladder cancer stem cells,and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients.METHODS:(1)CD44^(+)5637 bladder cancer stem cells were isolated by magnetic active cell sorting.Cancer stem cellrelated gene expression of SOX2,OCT4,and NANOG was detected via real-time polymerase chain reaction.The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44^(+)cells.Keratin 6B expression was detected in CD44^(+)bladder cancer stem cells by real-time polymerase chain reaction.(2)The CD44^(+)5637 bladder cancer stem cells were divided into two groups.In the keratin 6B siRNA group,keratin 6B small interfering RNA was transfected into CD44^(+)bladder cancer stem cells.Untransfected CD44^(+)bladder cancer stem cells were used as the black control group.Cells were collected at 2 days post-transfection.The proliferation,migration,and selfrenewal capacity of keratin 6B siRNA CD44^(+)bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively.(3)Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B.(4)ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer.RESULTS AND CONCLUSION:(1)Cancer stem cell-related genes(SOX2,OCT4,NANOG)and keratin 6B expression was higher in CD44^(+)cells isolated by magnetic active cell sorting compared with CD44-cells(P<0.05).Cell proliferation,migration,and in vitro spheroid formation were significantly increased(P<0.05).Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44^(+)bladder cancer stem cells(P<0.05).(2)Compared with the blank control group,the proliferation and migration of CD44^(+)bladder cancer stem cells after transfection of keratin 6B small interfering RNA(P<0.05),and the number of tumorsphere significantly diminished(P<0.05);the expression of Notch1 and Hes1 mRNA increased(P<0.05).(3)Keratin 6B and CD44v6 were significantly different in bladder cancer tissue(P=0.006).The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B.(4)The results showed that keratin 6B was highly expressed in CD44^(+)bladder cancer stem cells,and could promote the proliferation,migration,and self-renewal capacity of bladder cancer stem cells.The high expression of keratin 6B contributes to improving the survival of bladder cancer patients.

摘要： Camellia sinensis(tea),one of the most popular commercial crops,is commonly applied in all parts of the world.The main active ingredients of tea include polyphenols,alkaloids,polysaccharides,amino acids,aroma and volatile constitutes,all of which are potentially responsible for the activities of tea.Stem cells(SCs)are the immature and undifferentiated cells by a varying capacity for proliferation,self-renewal and the capability to differentiate into one or more different derivatives with specialized function or maintain their stem cell phenotype.Herein,a thorough review is conducted of the functional mechanism on SCs by tea bioactive compounds.

摘要： Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.

摘要： BACKGROUND Currently,ongoing trials of mesenchymal stem cells(MSC)therapies for coronavirus disease 2019(COVID-19)have been reported.AIM In this study,we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients.METHODS Search terms included stem cell,MSC,umbilical cord blood,novel coronavirus,severe acute respiratory syndrome coronavirus-2 and COVID-19,applied to Pub Med,the Cochrane Controlled Trials Register,EMBASE and Web of Science.RESULTS A total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients.The analysis showed no significant decrease in C-reactive protein(CRP)levels after stem cell therapy(P=0.11).A reduction of D-dimer levels was also not observed in patients after stem cell administration(P=0.82).Furthermore,interleukin 6(IL-6)demonstrated no decrease after stem cell therapy(P=0.45).Finally,we investigated the overall survival(OS)rate after stem cell therapy in COVID-19 patients.There was a significant improvement in OS after stem cell therapy;the OS of enrolled patients who received stem cell therapy was 90.3%,whereas that of the control group was 79.8%(P=0.02).CONCLUSION Overall,our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP,D-dimer and IL-6,OS is improved.

摘要： Hematopoietic stem cell transplantation(HSCT)-sinusoidal obstruction syndrome(SOS),also known as veno-occlusive disease,is a clinical syndrome characterized by symptoms,such as right upper quadrant pain,jaundice,fluid retention,and hepatomegaly,and is caused by pre-treatment-related hepatotoxicity during the early stages after HSCT.Clinical diagnosis of HSCT-SOS is based on the revised Seattle or Baltimore standards.The revised standard by the European Society for Bone Marrow Transplantation in 2016 has good practicability and can be used in combination with these two standards.Eight studies have shown the value of liver stiffness measurement(LSM)in the early diagnosis of HSCT-SOS.Four studies investigated LSM specificity and sensitivity for the early diagnosis of HSCT-SOS.LSM can distinguish SOS from other post-HSCT complications,enabling a clear differential diagnosis.It has been shown that median LSM of patients with SOS is significantly higher than that of patients with other treatment-related liver complications(e.g.,acute cholecystitis,cholangitis,antifungal drug-related liver injury,liver graft-versus-host disease,isolated liver biochemical changes,and fulminant Epstein Barr virus related hepatitis reactivation).Therefore,the above data confirmed the utility of LSM and strongly suggested that LSM improves the positive predictive value of the SOS diagnostic clinical score after allogeneic HSCT.Early diagnosis of SOS is beneficial in preventing severe HSCT complications.

摘要： Cardiovascular diseases represent the world’s leading cause of death. In thisheterogeneous group of diseases, ischemic cardiomyopathies are the mostdevastating and prevalent, estimated to cause 17.9 million deaths per year.Despite all biomedical efforts, there are no effective treatments that can replacethe myocytes lost during an ischemic event or progression of the disease to heartfailure. In this context, cell therapy is an emerging therapeutic alternative to treatcardiovascular diseases by cell administration, aimed at cardiac regeneration andrepair. In this review, we will cover more than 30 years of cell therapy in cardiology,presenting the main milestones and drawbacks in the field and signalingfuture challenges and perspectives. The outcomes of cardiac cell therapies arediscussed in three distinct aspects: The search for remuscularization byreplacement of lost cells by exogenous adult cells, the endogenous stem cell era,which pursued the isolation of a progenitor with the ability to induce heart repair,and the utilization of pluripotent stem cells as a rich and reliable source ofcardiomyocytes. Acellular therapies using cell derivatives, such as microvesiclesand exosomes, are presented as a promising cell-free therapeutic alternative.

摘要： Tumor-initiating cells(TICs)or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation,progression,metastasis,and drug resistance.It is hypothesized that gastrointestinal TICs(giTICs)might originate from cell-cell fusion.Here,we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo.We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells.Under this restriction,there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo.However,there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells.In addition,the mechanisms of giTIC generation via cell-cell fusion are poorly understood,and thus,we propose its potential mechanisms of action.We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo,isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells,and further clarification of the underlying mechanisms.Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.

摘要： Stem cell-based therapy raises hopes for a better approach to promoting tissue repair and functional recovery.However,transplanted stem cells show a high death percentage,creating challenges to successful transplantation and prognosis.Thus,it is necessary to investigate the mechanisms underlying stem cell death,such as apoptotic cascade activation,excessive autophagy,inflammatory response,reactive oxygen species,excitotoxicity,and ischemia/hypoxia.Targeting the molecular pathways involved may be an efficient strategy to enhance stem cell viability and maximize transplantation success.Notably,a more complex network of cell death receives more attention than one crucial pathway in determining stem cell fate,highlighting the challenges in exploring mechanisms and therapeutic targets.In this review,we focus on programmed cell death in transplanted stem cells.We also discuss some promising strategies and challenges in promoting survival for further study.

摘要： BACKGROUND Hypoxic-ischemic encephalopathy(HIE)is one of the leading causes of death and long-term neurological impairment in the pediatric population.Despite a limited number of treatments to cure HIE,stem cell therapies appear to be a potential treatment option for brain injury resulting from HIE.AIM To investigate the efficacy and safety of stem cell-based therapies in pediatric patients with HIE.METHODS The study inclusion criteria were determined as the presence of substantial deficit and disability caused by HIE.Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)were intrathecally(IT),intramuscularly(IM),and intravenously administered to participants at a dose of 1×10^(6)/kg for each administration route twice monthly for 2 mo.In different follow-up durations,the effect of WJ-MSCs administration on HIE,the quality of life,prognosis of patients,and side effects were investigated,and patients were evaluated for neurological,cognitive functions,and spasticity using the Wee Functional Independence Measure(Wee FIM)Scale and Modified Ashworth(MA)Scale.RESULTS For all participants(n=6),the mean duration of exposure to hypoxia was 39.17+18.82 min,the mean time interval after HIE was 21.83±26.60 mo,the mean baseline Wee FIM scale score was 13.5±0.55,and the mean baseline MA scale score was 35±9.08.Three patients developed only early complications such as low-grade fever,mild headache associated with IT injection,and muscle pain associated with IM injection,all of which were transient and disappeared within 24 h.The treatment was evaluated to be safe and effective as demonstrated by magnetic resonance imaging examinations,electroencephalographies,laboratory tests,and neurological and functional scores of patients.Patients exhibited significant improvements in all neurological functions through a 12-mo follow-up.The mean Wee FIM scale score of participants increased from 13.5±0.55 to 15.17±1.6 points(mean±SD)at 1 mo(z=-1.826,P=0.068)and to 23.5±3.39 points at 12 mo(z=-2.207,P=0.027)post-treatment.The percentage of patients who achieved an excellent functional improvement(Wee FIM scale total score=126)increased from 10.71%(at baseline)to 12.03%at 1 mo and to 18.65%at 12 mo posttreatment.CONCLUSION Both the triple-route and multiple WJ-MSC implantations were safe and effective in pediatric patients with HIE with significant neurological and functional improvements.The results of this study support conducting further randomized,placebo-controlled studies on this treatment in the pediatric population.