BACKGROUND Alopecia areata(AA)is a common autoimmune disease characterized by hair loss.AA appears in extensive forms,such as progressive and diffusing hair loss(diffuse AA),a total loss of scalp hair(alopecia totalis...BACKGROUND Alopecia areata(AA)is a common autoimmune disease characterized by hair loss.AA appears in extensive forms,such as progressive and diffusing hair loss(diffuse AA),a total loss of scalp hair(alopecia totalis),and complete loss of hair over the entire body(alopecia universalis).Recently,mesenchymal stem cells(MSCs)have been identified as a therapeutic alternative for autoimmune diseases.For this reason,preclinical and case studies of AA and related diseases using MSCs have been conducted.CASE SUMMARY Case 1:A 55-year-old woman suffered from AA in two areas of the scalp.She was given 15 rounds of minimally manipulated umbilical cord-MSCs(MM-UC-MSCs)over 6 mo.The AA gradually improved 3 mo after the first round.The patient was cured,and AA did not recur.Case 2:A 30-year-old woman,with history of local steroid hormone injections,suffered from AA in one area on the scalp.She was given two rounds of MM-UC-MSCs over 1 mo.The AA immediately improved after the first round.The patient was cured,and AA did not recur.Case 3:A 20-year-old woman,who was diagnosed with alopecia universalis at the age of 12,was given 14 rounds of MM-UC-MSCs over 12 mo.Her hair began to grow about 3 mo after the first round.The patient was cured,and alopecia universalis did not recur.CONCLUSION MM-UC-MSC transplantation potentially treats patients who suffer from AA and related diseases.展开更多
Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs...Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.展开更多
BACKGROUND： MicroRNA （miRNA） expression in stem cells provides important clues for the molecular mechanisms of stem cell proliferation and differentiation. Bone marrow stromal cells and spinal cord-derived neural s...BACKGROUND： MicroRNA （miRNA） expression in stem cells provides important clues for the molecular mechanisms of stem cell proliferation and differentiation. Bone marrow stromal cells and spinal cord-derived neural stem cells exhibit potential for neural regeneration. However, miRNA expression in these cells has been rarely reported. OBJECTIVE： To explore differential expression of two nervous system-specific miRNAs, miR-124 and miR-128, in bone marrow stromal cells and spinal cord-derived neural stem cells. DESIGN, TIME AND SETTING： An In vitro, cell biology experiment was performed at the Department of Biotechnology, Shanxi Medical University from June 2008 to June 2009. MATERIALS： TaqMan miRNA assays were purchased from Applied Biosystems. METHODS： Rat bone marrow stromal cells were isolated and cultured using the whole-bone marrow method, and rat spinal cord-derived neural stem cells were obtained through neurosphere formation. TaqMan miRNA assays were used to measure miR-124 and miR-128 expression in bone marrow stromal cells and spinal cord-derived neural stem cells. MAIN OUTCOME MEASURES： Morphology of bone marrow stromal cells and spinal cord-derived neural stem cells were observed by inverted microscopy. Expression of the neural stem cell-specific marker, nestin, the bone marrow stromal cell surface marker, CD71, and expression of miR-124 and miR-128, were detected by real-time polymerase chain reaction. RESULTS： Cultured bone marrow stromal cells displayed a short fusiform shape. Flow cytometry revealed a large number of CD71-positive cells （〉 95%）. Cultured spinal cord-derived neural stem cells formed nestin-positive neurospheres, and quantitative detection of miRNA demonstrated that less miR-124 and miR-128 was expressed in bone marrow stromal cells compared to spinal cord-derived neural stem cells （P 〈 0.05）. CONCLUSION： Bone marrow stromal cells and spinal cord-derived neural stem cells exhibited differential expression of miR-124 and miR-128, which suggested different characteristics in miRNA expression.展开更多
BACKGROUND Stroke is one of the major causes of disability and death worldwide.Some treatments for stroke exist,but existing treatment methods have limitations such as difficulty in the regeneration of damaged neurona...BACKGROUND Stroke is one of the major causes of disability and death worldwide.Some treatments for stroke exist,but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain.Recently,mesenchymal stem cells(MSCs)have been studied as a therapeutic alternative for stroke,and various preclinical and case studies have been reported.CASE SUMMARY A 55-year-old man suffered an acute stroke,causing paralysis in the left upper and lower limbs.He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs(MM-UC-MSCs)twice with an 8-d interval.At 65 wk after transplantation,the patient returned to his previous occupation as a veterinarian with no adverse reactions.CONCLUSION MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.展开更多
AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on fou...AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017.HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg.Clinical response,relapse rate,change of visual acuity,and other metrics were evaluated.RESULTS:All four patients presented with responses to HUC-MSCs treatment,with three males and one female.The numbers of uveitis attacks per year after the HUCMSCs treatment(0,2,0,0 respectively)all decreased compared with the numbers before the treatment(3,6,4,4 respectively).The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation,and three patients discontinued their oral medicine at the last visit.The best corrected visual acuity(BCVA)of 3 patients was improved to varying degrees,and the BCVA of 1 patient remained at 20/20(Snellen chart)from the first to the last consultation.CONCLUSION:The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.展开更多
CD34+cells differentiated from mesenchymal stem cells (MSCs) have a strong biological function in cardiovascular regeneration. However, the molecular mechanisms of and the methods to improve the CD34+ cell differentia...CD34+cells differentiated from mesenchymal stem cells (MSCs) have a strong biological function in cardiovascular regeneration. However, the molecular mechanisms of and the methods to improve the CD34+ cell differentiation from MSCs, especially from human MSCs (hUC-MSCs) are still unclear. In the current study, the effect of CD34 antibody on the CD34+ cell differentiation from human umbilical cord (UC)-derived MSCs (hUC-MSCs) is determined. The results have demonstrated that the expression of cd34 protein is significantly increased in hUC-MSCs treated with CD34 antibody. In addition, the cell proliferation is increased in hUC-MSCs after treatment with CD34 antibody. Moreover, the expression of PI3K, AKT, p-AKT proteins, which are signaling molecules related to stem cell differentiation, is increased by CD34 antibody. The results suggest that CD34 antibody could promote the differentiation of hUC-MSCs into CD34+ cells and PI3K/AKT may be involved in this important process.展开更多
Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. In...Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.展开更多
Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this dise...Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.展开更多
In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a n...In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a new treatment approach as“Living Biodrugs”.HF remains a significant clinical challenge due to the heart’s inability to pump blood effectively,despite advancements in medical and device-based therapies.MSCs have emerged as a promising therapeutic approach,offering benefits beyond traditional treatments through their ability to modulate inflammation,reduce fibrosis,and promote endogenous tissue rege-neration.MSCs can be derived from various tissues,including bone marrow and umbilical cord.Umbilical cord-derived MSCs exhibit superior expansion ca-pabilities,making them an attractive option for HF therapy.Conversely,bone marrow-derived MSCs have been extensively studied for their potential to im-prove cardiac function but face challenges related to cell retention and delivery.Future research is focusing on optimizing MSC sources,enhancing differentiation and immune modulation,and improving delivery methods to overcome current limitations.展开更多
Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffol...Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.展开更多
Human umbilical cord-derived mesenchymal stem cells （hUCMSCs） represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regen...Human umbilical cord-derived mesenchymal stem cells （hUCMSCs） represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the para-crine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These ifndings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.展开更多
Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells ...Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells （HUC-MSCs）, which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice （saline and HEK293 cells injections were performed in a separate set of mice） and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression （2-8 fold） in HUC-MSCs injected testes compared to the contralateral uninjected testes （five mice）. Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein （Scp3） were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.展开更多
BACKGROUND Psoriasis is a chronic autoimmune disease that usually manifests as a red scaly epidermis,induration,and hyperproliferation of basal keratinocytes.About 2%of the world’s population suffers from psoriasis b...BACKGROUND Psoriasis is a chronic autoimmune disease that usually manifests as a red scaly epidermis,induration,and hyperproliferation of basal keratinocytes.About 2%of the world’s population suffers from psoriasis but there are no clear therapeutics yet.Recently,mesenchymal stem cells(MSCs)have been regarded as a therapeutic alternative for autoimmune diseases,as they possess immunosuppressive effects without risks.Human umbilical cord-derived MSCs effectively regulate immune cells and are characterized by low immunogenicity,which has many advantages in treating immune diseases.CASE SUMMARY The patient was a 47-year-old male,diagnosed with psoriasis in 1995.He had received various treatments for 25 years,but the psoriatic condition was not significantly improved.He was given three rounds of minimally manipulated umbilical cord-derived MSCs over 2 wk.The erythema gradually disappeared.Three months after the 1st round,all erythema completely disappeared,and the psoriasis did not recur.CONCLUSION Minimally manipulated umbilical cord-derived MSC transplantation can potentially treat patients who suffer from psoriasis.展开更多
Ideal tissue-engineered scaffold materials regulate proliferation, apoptosis and differentiation of cells seeded on them by regulating gene expression. In this study, aligned and randomly oriented collagen nanofiber s...Ideal tissue-engineered scaffold materials regulate proliferation, apoptosis and differentiation of cells seeded on them by regulating gene expression. In this study, aligned and randomly oriented collagen nanofiber scaffolds were prepared using electronic spinning technology. Their diameters and appearance reached the standards of tissue-engineered nanometer scaffolds. The nanofiber scaffolds were characterized by a high swelling ratio, high porosity and good mechanical properties. The proliferation of spinal cord-derived neural stem cells on novel nanofiber scaffolds was obviously enhanced. The proportions of cells in the S and G2/M phases noticeably increased. Moreover, the proliferation rate of neural stem cells on the aligned collagen nanofiber scaffolds was high. The expression levels of cyclin D1 and cyclin-dependent kinase 2 were increased. Bcl-2 expression was significantly increased, but Bax and caspase-3 gene expressions were obviously decreased. There was no significant difference in the differentiation of neural stem cells into neurons on aligned and randomly oriented collagen nanofiber scaffolds. These results indicate that novel nanofiber scaffolds could promote the proliferation of spinal cord-derived neural stem cells and inhibit apoptosis without inducing differentiation. Nanofiber scaffolds regulate apoptosis and proliferation in neural stem cells by altering gene expression.展开更多
Coronavirus disease-2019(COVID-19)has affected more than 200 countries worldwide.This disease has hugely affected healthcare systems as well as the economy to an extent never seen before.To date,COVID-19 infection has...Coronavirus disease-2019(COVID-19)has affected more than 200 countries worldwide.This disease has hugely affected healthcare systems as well as the economy to an extent never seen before.To date,COVID-19 infection has led to about 165000 deaths in 150 countries.At present,there is no specific drug or efficient treatment for this disease.In this analysis based on evidential relationships of the biological characteristics of MSCs,especially umbilical cord(UC)-derived MSCs as well as the first clinical trial using MSCs for COVID-19 treatment,we discuss the use of UC-MSCs to improve the symptoms of COVID-19 in patients.展开更多
This study established superparamagnetic iron oxide （SPIO）-labeled nerve growth fac-tor-β （NGF-β） gene-modified spinal cord-derived neural stem cells （NSCs）. The El4 rat embryonic spinal cord-derived NSCs were...This study established superparamagnetic iron oxide （SPIO）-labeled nerve growth fac-tor-β （NGF-β） gene-modified spinal cord-derived neural stem cells （NSCs）. The El4 rat embryonic spinal cord-derived NSCs were isolated and cultured. The cells of the third passage were transfected with plasmid pcDNA3-hNGFβ by using FuGENE HD transfection reagent. The expression of NGFβ was measured by immunocytochemistry and Western blotting. The positive clones were selected, allowed to proliferate and then labeled with SPIO, which was mediated by FuGENE HD transfection reagent. Prussian blue staining and transmission electron microscopy （TEM） were used to identify the SPIO particles in the cells. The distinctive markers for stem cells （nestin）, neuron （β-Ⅲ-tubulin）, oligodendrocyte （CNPase） and astrocyte （GFAP） were employed to evaluate the differentiation ability of the labeled cells. The immunocytochemistry and western blotting showed that NGF-β was expressed in spinal cord-derived NSCs. Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells. TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma. The immunocytochemistry demonstrated that the labeled cells were nestin-positive. After differentiation, the cells expressed β-Ⅲ-tubulin, CNPase and GFAP. It was concluded that the SPIO-labeled NGF-β gene-modified spinal cord-derived NSC were successfully established, which are multipotent and capable of self-renewal.展开更多
Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore...Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.展开更多
文摘BACKGROUND Alopecia areata(AA)is a common autoimmune disease characterized by hair loss.AA appears in extensive forms,such as progressive and diffusing hair loss(diffuse AA),a total loss of scalp hair(alopecia totalis),and complete loss of hair over the entire body(alopecia universalis).Recently,mesenchymal stem cells(MSCs)have been identified as a therapeutic alternative for autoimmune diseases.For this reason,preclinical and case studies of AA and related diseases using MSCs have been conducted.CASE SUMMARY Case 1:A 55-year-old woman suffered from AA in two areas of the scalp.She was given 15 rounds of minimally manipulated umbilical cord-MSCs(MM-UC-MSCs)over 6 mo.The AA gradually improved 3 mo after the first round.The patient was cured,and AA did not recur.Case 2:A 30-year-old woman,with history of local steroid hormone injections,suffered from AA in one area on the scalp.She was given two rounds of MM-UC-MSCs over 1 mo.The AA immediately improved after the first round.The patient was cured,and AA did not recur.Case 3:A 20-year-old woman,who was diagnosed with alopecia universalis at the age of 12,was given 14 rounds of MM-UC-MSCs over 12 mo.Her hair began to grow about 3 mo after the first round.The patient was cured,and alopecia universalis did not recur.CONCLUSION MM-UC-MSC transplantation potentially treats patients who suffer from AA and related diseases.
基金the National Natural Science Foundation of China,No.81471308(to JL)Stem cell Clinical Research Registry Program,No.CMR-20161129-1003(to JL)+2 种基金Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031(to JL)Dalian Innovation Fund of China,No.2018J11CY025(to JL)National Defense Science and Technology New Special Zone Contract,No.19-163-00-kx-003-001-01(to JL)。
文摘Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.
基金the National Natural Science Foundation of China, No. 30672114
文摘BACKGROUND： MicroRNA （miRNA） expression in stem cells provides important clues for the molecular mechanisms of stem cell proliferation and differentiation. Bone marrow stromal cells and spinal cord-derived neural stem cells exhibit potential for neural regeneration. However, miRNA expression in these cells has been rarely reported. OBJECTIVE： To explore differential expression of two nervous system-specific miRNAs, miR-124 and miR-128, in bone marrow stromal cells and spinal cord-derived neural stem cells. DESIGN, TIME AND SETTING： An In vitro, cell biology experiment was performed at the Department of Biotechnology, Shanxi Medical University from June 2008 to June 2009. MATERIALS： TaqMan miRNA assays were purchased from Applied Biosystems. METHODS： Rat bone marrow stromal cells were isolated and cultured using the whole-bone marrow method, and rat spinal cord-derived neural stem cells were obtained through neurosphere formation. TaqMan miRNA assays were used to measure miR-124 and miR-128 expression in bone marrow stromal cells and spinal cord-derived neural stem cells. MAIN OUTCOME MEASURES： Morphology of bone marrow stromal cells and spinal cord-derived neural stem cells were observed by inverted microscopy. Expression of the neural stem cell-specific marker, nestin, the bone marrow stromal cell surface marker, CD71, and expression of miR-124 and miR-128, were detected by real-time polymerase chain reaction. RESULTS： Cultured bone marrow stromal cells displayed a short fusiform shape. Flow cytometry revealed a large number of CD71-positive cells （〉 95%）. Cultured spinal cord-derived neural stem cells formed nestin-positive neurospheres, and quantitative detection of miRNA demonstrated that less miR-124 and miR-128 was expressed in bone marrow stromal cells compared to spinal cord-derived neural stem cells （P 〈 0.05）. CONCLUSION： Bone marrow stromal cells and spinal cord-derived neural stem cells exhibited differential expression of miR-124 and miR-128, which suggested different characteristics in miRNA expression.
文摘BACKGROUND Stroke is one of the major causes of disability and death worldwide.Some treatments for stroke exist,but existing treatment methods have limitations such as difficulty in the regeneration of damaged neuronal cells of the brain.Recently,mesenchymal stem cells(MSCs)have been studied as a therapeutic alternative for stroke,and various preclinical and case studies have been reported.CASE SUMMARY A 55-year-old man suffered an acute stroke,causing paralysis in the left upper and lower limbs.He intravenously transplanted the minimally manipulated human umbilical cord-derived MSCs(MM-UC-MSCs)twice with an 8-d interval.At 65 wk after transplantation,the patient returned to his previous occupation as a veterinarian with no adverse reactions.CONCLUSION MM-UC-MSCs transplantation potentially treats patients who suffer from acute ischemic stroke.
文摘AIM:To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells(HUC-MSCs)treatment in patients with refractory uveitis.METHODS:A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017.HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg.Clinical response,relapse rate,change of visual acuity,and other metrics were evaluated.RESULTS:All four patients presented with responses to HUC-MSCs treatment,with three males and one female.The numbers of uveitis attacks per year after the HUCMSCs treatment(0,2,0,0 respectively)all decreased compared with the numbers before the treatment(3,6,4,4 respectively).The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation,and three patients discontinued their oral medicine at the last visit.The best corrected visual acuity(BCVA)of 3 patients was improved to varying degrees,and the BCVA of 1 patient remained at 20/20(Snellen chart)from the first to the last consultation.CONCLUSION:The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.
文摘CD34+cells differentiated from mesenchymal stem cells (MSCs) have a strong biological function in cardiovascular regeneration. However, the molecular mechanisms of and the methods to improve the CD34+ cell differentiation from MSCs, especially from human MSCs (hUC-MSCs) are still unclear. In the current study, the effect of CD34 antibody on the CD34+ cell differentiation from human umbilical cord (UC)-derived MSCs (hUC-MSCs) is determined. The results have demonstrated that the expression of cd34 protein is significantly increased in hUC-MSCs treated with CD34 antibody. In addition, the cell proliferation is increased in hUC-MSCs after treatment with CD34 antibody. Moreover, the expression of PI3K, AKT, p-AKT proteins, which are signaling molecules related to stem cell differentiation, is increased by CD34 antibody. The results suggest that CD34 antibody could promote the differentiation of hUC-MSCs into CD34+ cells and PI3K/AKT may be involved in this important process.
文摘Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.
基金partially supported by the Science and Technology Research Program of Chongqing Municipality Education Commision(No.KJQN201800407).
文摘Severe bronchopulmonary dysplasia(BPD)is a chronic lung disorder that primarily affects premature babies with extremely low birth weight and involves in multiple organ system;no effective pharmacotherapy for this disease exists,and mortality remains high.Based on the evidence from previous preclinical studies and phase I clinical trials,this study aims to test the safety of intravenous application of a single dose of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in patients with severe BPD.The Mesenchymal Stem cells for Bronchopulmonary Dysplasia Treatment(MSBDT)trial is a single center,open-label,dose-escalation phase I clinical trial.Severe BPD patients were enrolled in Children Hospital of Chongqing Medical University,Chongqing,China.The first six patients were treated with low-dose hUC-MSCs(1×10^(6) cells/kg)and the next seven patients were treated with high-dose hUC-MSCs(5×10^(6) cells/kg).This study is registered with ClinicalTrials.gov,number NCT03558334.No prespecified infusion-associated adverse events,immediate complication,respiratory or cardiovascular compromise were observed during infusion and 24 h after infusion.No significant changes in safety laboratory values were observed.One death event occurred in the low-dose group on study day 10,and one death event occurred in the high-dose group on study day 24,while,after review in detail,the two cases are not believed to be infusion-associated events.In conclusion,intravenous application of a single dose of hUC-MSCs was tolerated in thirteen patients with severe BPD.
文摘In this editorial we comment on the article by Safwan M et al.We especially fo-cused on the cardiac function restoration by the use of mesenchymal stem cells(MSCs)therapy for heart failure(HF),which has emerged as a new treatment approach as“Living Biodrugs”.HF remains a significant clinical challenge due to the heart’s inability to pump blood effectively,despite advancements in medical and device-based therapies.MSCs have emerged as a promising therapeutic approach,offering benefits beyond traditional treatments through their ability to modulate inflammation,reduce fibrosis,and promote endogenous tissue rege-neration.MSCs can be derived from various tissues,including bone marrow and umbilical cord.Umbilical cord-derived MSCs exhibit superior expansion ca-pabilities,making them an attractive option for HF therapy.Conversely,bone marrow-derived MSCs have been extensively studied for their potential to im-prove cardiac function but face challenges related to cell retention and delivery.Future research is focusing on optimizing MSC sources,enhancing differentiation and immune modulation,and improving delivery methods to overcome current limitations.
基金supported by the National Key Research and Development Plan of China,No.2016YFC1101500 (to ZS)the National Natural Science Foundation of China,Nos.11932013 and 11672332 (both to XYC)。
文摘Animal expe riments have shown that injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can promote recovery from spinal cord injury.To investigate whether injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells can be used to treat spontaneous intracerebral hemorrhage,this non-randomized phase I clinical trial recruited patients who met the inclusion criteria and did not meet the exclusion crite ria of spontaneous intracerebral hemorrhage treated in the Characteristic Medical Center of Chinese People’s Armed Police Force from May 2016 to December 2020.Patients were divided into three groups according to the clinical situation and patient benefit:control(n=18),human umbilical cord-derived mesenchymal stem cells(n=4),and combination(n=8).The control group did not receive any transplantation.The human umbilical cord-derived mesenchymal stem cells group received human umbilical cord-derived mesenchymal stem cell transplantation.The combination group received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells.Patients who received injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells had more remarkable improvements in activities of daily living and cognitive function and smaller foci of intra cerebral hemorrhage-related encephalomalacia.Severe adve rse events associated with cell transplantation were not observed.Injectable collagen scaffold with human umbilical cord-derived mesenchymal stem cells appears to have great potential treating spontaneous intracerebral hemorrhage.
基金supported by the National Natural Science Foundation of China,No.31100696,31170946a grant from the National High Technology Research and Development Program of China(863 Program),No.2012AA020502+1 种基金a grant from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542201a grant from Beijing Metropolis Beijing Nova Program,No.2011115
文摘Human umbilical cord-derived mesenchymal stem cells （hUCMSCs） represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the para-crine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These ifndings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.
文摘Various methods are currently under investigation to preserve fertility in males treated with high-dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells （HUC-MSCs）, which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC-MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efficiently. HUC-MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan-treated mice （saline and HEK293 cells injections were performed in a separate set of mice） and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression （2-8 fold） in HUC-MSCs injected testes compared to the contralateral uninjected testes （five mice）. Protein levels for germ cell-specific genes, miwi, vasa and synaptonemal complex protein （Scp3） were also higher in MSC-treated testes compared to injected controls 3 weeks after treatment. However, no different expression was detected in saline water and HEK293 cells injection control group. We have demonstrated HUC-MSCs could affect mouse germ cell-specific genes expression. The results also provide a possibility that the transplanted HUC-MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC-MSCs, and explores a new approach to the treatment of azoospermia.
文摘BACKGROUND Psoriasis is a chronic autoimmune disease that usually manifests as a red scaly epidermis,induration,and hyperproliferation of basal keratinocytes.About 2%of the world’s population suffers from psoriasis but there are no clear therapeutics yet.Recently,mesenchymal stem cells(MSCs)have been regarded as a therapeutic alternative for autoimmune diseases,as they possess immunosuppressive effects without risks.Human umbilical cord-derived MSCs effectively regulate immune cells and are characterized by low immunogenicity,which has many advantages in treating immune diseases.CASE SUMMARY The patient was a 47-year-old male,diagnosed with psoriasis in 1995.He had received various treatments for 25 years,but the psoriatic condition was not significantly improved.He was given three rounds of minimally manipulated umbilical cord-derived MSCs over 2 wk.The erythema gradually disappeared.Three months after the 1st round,all erythema completely disappeared,and the psoriasis did not recur.CONCLUSION Minimally manipulated umbilical cord-derived MSC transplantation can potentially treat patients who suffer from psoriasis.
文摘Ideal tissue-engineered scaffold materials regulate proliferation, apoptosis and differentiation of cells seeded on them by regulating gene expression. In this study, aligned and randomly oriented collagen nanofiber scaffolds were prepared using electronic spinning technology. Their diameters and appearance reached the standards of tissue-engineered nanometer scaffolds. The nanofiber scaffolds were characterized by a high swelling ratio, high porosity and good mechanical properties. The proliferation of spinal cord-derived neural stem cells on novel nanofiber scaffolds was obviously enhanced. The proportions of cells in the S and G2/M phases noticeably increased. Moreover, the proliferation rate of neural stem cells on the aligned collagen nanofiber scaffolds was high. The expression levels of cyclin D1 and cyclin-dependent kinase 2 were increased. Bcl-2 expression was significantly increased, but Bax and caspase-3 gene expressions were obviously decreased. There was no significant difference in the differentiation of neural stem cells into neurons on aligned and randomly oriented collagen nanofiber scaffolds. These results indicate that novel nanofiber scaffolds could promote the proliferation of spinal cord-derived neural stem cells and inhibit apoptosis without inducing differentiation. Nanofiber scaffolds regulate apoptosis and proliferation in neural stem cells by altering gene expression.
文摘Coronavirus disease-2019(COVID-19)has affected more than 200 countries worldwide.This disease has hugely affected healthcare systems as well as the economy to an extent never seen before.To date,COVID-19 infection has led to about 165000 deaths in 150 countries.At present,there is no specific drug or efficient treatment for this disease.In this analysis based on evidential relationships of the biological characteristics of MSCs,especially umbilical cord(UC)-derived MSCs as well as the first clinical trial using MSCs for COVID-19 treatment,we discuss the use of UC-MSCs to improve the symptoms of COVID-19 in patients.
基金supported by a grant from the National Natural Sciences Foundation of China (No.30672151)
文摘This study established superparamagnetic iron oxide （SPIO）-labeled nerve growth fac-tor-β （NGF-β） gene-modified spinal cord-derived neural stem cells （NSCs）. The El4 rat embryonic spinal cord-derived NSCs were isolated and cultured. The cells of the third passage were transfected with plasmid pcDNA3-hNGFβ by using FuGENE HD transfection reagent. The expression of NGFβ was measured by immunocytochemistry and Western blotting. The positive clones were selected, allowed to proliferate and then labeled with SPIO, which was mediated by FuGENE HD transfection reagent. Prussian blue staining and transmission electron microscopy （TEM） were used to identify the SPIO particles in the cells. The distinctive markers for stem cells （nestin）, neuron （β-Ⅲ-tubulin）, oligodendrocyte （CNPase） and astrocyte （GFAP） were employed to evaluate the differentiation ability of the labeled cells. The immunocytochemistry and western blotting showed that NGF-β was expressed in spinal cord-derived NSCs. Prussian blue staining indicated that numerous blue-stained particles appeared in the cytoplasma of the labeled cells. TEM showed that SPIO particles were found in vacuolar structures of different sizes and the cytoplasma. The immunocytochemistry demonstrated that the labeled cells were nestin-positive. After differentiation, the cells expressed β-Ⅲ-tubulin, CNPase and GFAP. It was concluded that the SPIO-labeled NGF-β gene-modified spinal cord-derived NSC were successfully established, which are multipotent and capable of self-renewal.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81891002,No.32071338)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040702,XDA16040704)+1 种基金National Key R&D Program of China(2017YFA0104701,2017YFA0104704)CAS Project for Young Scientists in Basic Research(YSRB073).
文摘Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.
