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Controversies regarding transplantation of mesenchymal stem cells
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作者 Tsvetelina Velikova Tereza Dekova Dimitrina Georgieva Miteva 《World Journal of Transplantation》 2024年第2期48-61,共14页
Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intric... Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation. 展开更多
关键词 mesenchymal stem cells transplantation controversies Regenerative medicine Autoimmune diseases Chronic inflammatory illnesses Tumor growth METASTASIS Therapeutic potential Clinical use of mesenchymal stem cell
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Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model 被引量:42
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作者 Wan, Chi-Dan Cheng, Rui +1 位作者 Wang, Hong-Bo Liu, Tao 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2008年第1期29-33,共5页
BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for prevent... BACKGROUND: Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation. METHODS: MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed. RESULTS: In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2 +/- 45.0 U/L, 162.5 +/- 30.5 U/L, 30.6 +/- 5.4 mu mol/L, 187.35 +/- 18.26 mu g/L and 193.95 +/- 37.62 mu g/L, and those in the blank control group were 355.6 +/- 54.3 U/L, 296.4 +/- 71.2 U/L, 145.7 +/- 28.6 +/- mol/L, 295.73 +/- 57.15 mu g/L and 75.12 +/- 11.23 mu g/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05). CONCLUSION: Adipose-derived MSCs clearly inhibit recipient-derived T lymphocyte proliferation in MLC and significantly alleviate acute rejection following orthotopic liver transplantation in rats. 展开更多
关键词 adipose tissue mesenchymal stem cells liver transplantation acute rejection
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Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation 被引量:9
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作者 Liu Yang Zhong-Yang Shen +5 位作者 Rao-Rao Wang Ming-Li Yin Wei-Ping Zheng Bin Wu Tao Liu Hong-Li Song 《World Journal of Gastroenterology》 SCIE CAS 2017年第19期3449-3467,共19页
AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantati... AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver. 展开更多
关键词 Reduced-size liver transplantation Bone marrow mesenchymal stem cells MICROCIRCULATION Heme oxygenase-1 Energy metabolism
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Magnetically labeled mesenchymal stem cells after autologous transplantation into acutely injured liver 被引量:5
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作者 Xiao-Lei Shi Jin-Yang Gu +3 位作者 Bing Han Hai-Yun Xu Liang Fang Yi-Tao Ding 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第29期3674-3679,共6页
AIM:To evaluate tracking of magnetically labeled mesenchymal stem cells(MSCs) after intraportal transplantation.METHODS:Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifuga... AIM:To evaluate tracking of magnetically labeled mesenchymal stem cells(MSCs) after intraportal transplantation.METHODS:Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifugation,cultured and expanded,after which,they were incubated with super paramagnetic iron oxide(SPIO).Prussian blue staining was performed to highlight intracellular iron.To establish swine models of acute liver injury,0.5 g/kg D-galactosamine was administrated to 10 pigs,six of which were injected via their portal veins with SPIO-labeled MSCs,while the remaining four were injected with unlabeled cells.Magnetic resonance imaging(MRI) was performed with a clinical 1.5T MR scanner immediately before transplantation and 6 h,3 d,7 d and 14 d after transplantation.Prussian blue staining was again performed with the tissue slices at the endpoint.RESULTS:Prussian blue staining of SPIO-labeled MSCs had a labeling efficiency of almost 100%.Signal intensity loss in the liver by SPIO labeling on the FFE(T2*WI) sequence persisted until 14 d after transplantation.Histological analysis by Prussian blue staining confirmed homing of labeled MSCs in the liver after 14 d;primarily distributed in hepatic sinusoids and liver parenchyma.CONCLUSION:MSCs were successfully labeled with SPIO in vitro.MRI can monitor magnetically labeled MSCs transplanted into the liver. 展开更多
关键词 Magnetic resonance imaging mesenchymal stem cells Super paramagnetic iron oxide stem cell transplantation
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Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats 被引量:71
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作者 Dong-ChangZhao Jun-XiaLei +4 位作者 RuiChen Wei-HuaYu Xiu-MingZhang Shu-NongLi PengXiang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第22期3431-3440,共10页
AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing infl... AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats. METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCI4) or dimethylnitrosamine (DMN). There were two random groups on the 42nd d of CCI4: CCl4/MSCs, to infuse a dose of MSCs alone; CCI4/saline, to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR. RESULTS: Compared to controls, infusion of MSCs reduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (20-40% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR. CONCLUSION: MSCs treatment can protect against experimental liver fibrosis in CCMnduced or DMN-induced rats and the mechanisms of the anti-fibrosis by MSCs will be studied further. 展开更多
关键词 mesenchymal stem cells liver fibrosis RAT THERAPY
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In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis 被引量:20
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作者 Guo-Zun Zhang Hui-Cong Sun +2 位作者 Li-Bo Zheng Jin-Bo Guo Xiao-Lan Zhang 《World Journal of Gastroenterology》 SCIE CAS 2017年第46期8152-8168,共17页
AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.METHODS A CCl4-induced li... AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of h UC-MSCs. Histopathology was assessed by hematoxylin and eosin(H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.RESULTS We demonstrated that the infused h UC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of h UC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted h UC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. h UC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. 展开更多
关键词 liver fibrosis/cirrhosis mesenchymal stem cells Collagen metabolism HEPATOCYTE DIFFERENTIATION
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Intravenous injection of mesenchymal stem cells is effective in treating liver fibrosis 被引量:32
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作者 Wei Zhao Jun-Jie Li +6 位作者 Da-Yong Cao Xiao Li Lin-Ying Zhang Yong He Shu-Qiang Yue De-Sheng Wang Ke-Feng Dou 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第10期1048-1058,共11页
AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyt... AIM: To compare the influence of different transplant sites in bone marrow mesenchymal stem cell (MSC)-based therapy for liver fibrosis. METHODS: MSCs isolated from Sprague Dawley (SD) rats were induced into hepatocyte-like cells. Liver fibrosis in SD rats was induced with carbon tetrachloride. Following hepatocyte induction in vitro, 4',6-diamidino- 2-phenylindole (DAPI)-labeled MSCs were transplanted by intravenous, intrahepatic, and intraperitoneal injection. Histopathological staining, immunohistochemistry, and biochemical analysis were used to compare the morphological and functional liver regeneration among different MSC injection modalities. The expression differences of interleukins, growth factor, extracellular matrix, matrix metalloproteinases, and tissue inhibitor of metalloproteinase were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR) andenzyme linked immunosorbent assay (ELISA). RESULTS: Four days after exposure to hepatocyte differentiation medium, MSCs that did not express hepatocyte markers could express α-fetoprotein, albumin, and cytokeratin 18. The results of histopathological staining, immunohistochemistry, and biochemical analysis indicated that intravenous injection is more effective at rescuing liver failure than other injection modalities. DAPI-labeled cells were found around liver lobules in all three injection site groups, but the intravenous group had the highest number of cells. PCR and ELISA analysis indicated that interleukin-10 (IL-10) was highest in the intravenous group, whereas il1β, il6, tnfα and tgfβ, which can be regulated by IL10 and are promoters of liver fibrosis, were significantly lower than in the other groups. CONCLUSION: MSC administration is able to protect against liver fibrosis. Intravenous injection is the most favorable treatment modality through promotion of IL10 expression. 展开更多
关键词 mesenchymal stem cells Hepatocyte differentiation Intravenous injection liver fibrosis INTERLEUKIN-10
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Therapeutic efficiency of bone marrow-derived mesenchymal stem cells for liver fibrosis:A systematic review of in vivo studies 被引量:3
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作者 Zaid Al-Dhamin Ling-Di Liu +3 位作者 Dong-Dong Li Si-Yu Zhang Shi-Ming Dong Yue-Min Nan 《World Journal of Gastroenterology》 SCIE CAS 2020年第47期7444-7469,共26页
Although multiple drugs are accessible for recovering liver function in patients,none are considered efficient.Liver transplantation is the mainstay therapy for end-stage liver fibrosis.However,the worldwide shortage ... Although multiple drugs are accessible for recovering liver function in patients,none are considered efficient.Liver transplantation is the mainstay therapy for end-stage liver fibrosis.However,the worldwide shortage of healthy liver donors,organ rejection,complex surgery,and high costs are prompting researchers to develop novel approaches to deal with the overwhelming liver fibrosis cases.Mesenchymal stem cell(MSC)therapy is an emerging alternative method for treating patients with liver fibrosis.However,many aspects of this therapy remain unclear,such as the efficiency compared to conventional treatment,the ideal MSC sources,and the most effective way to use it.Because bone marrow(BM)is the largest source for MSCs,this paper used a systematic review approach to study the therapeutic efficiency of MSCs against liver fibrosis and related factors.We systematically searched multiple published articles to identify studies involving liver fibrosis and BM-MSC-based therapy.Analyzing the selected studies showed that compared with conventional treatment BM-MSC therapy may be more efficient for liver fibrosis in some cases.In contrast,the cotreatment presented a more efficient way.Nevertheless,BM-MSCs are lacking as a therapy for liver fibrosis;thus,this paper also reviews factors that affect BM-MSC efficiency,such as the implementation routes and strategies employed to enhance the potential in alleviating liver fibrosis.Ultimately,our review summarizes the recent advances in the BM-MSC therapy for liver fibrosis.It is grounded in recent developments underlying the efficiency of BM-MSCs as therapy,focusing on the preclinical in vivo experiments,and comparing to other treatments or sources and the strategies used to enhance its potential while mentioning the research gaps. 展开更多
关键词 Bone marrow mesenchymal stem cells liver fibrosis In vivo EFFICIENCY
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Current perspectives on mesenchymal stem cells as a potential therapeutic strategy for non-alcoholic fatty liver disease 被引量:4
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作者 Yan Jiang Narazah Mohd Yusoff +2 位作者 Jiang Du Emmanuel Jairaj Moses Jun-Tang Lin 《World Journal of Stem Cells》 SCIE 2024年第7期760-772,共13页
Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially pre... Non-alcoholic fatty liver disease(NAFLD)has emerged as a significant health challenge,characterized by its widespread prevalence,intricate natural progression and multifaceted pathogenesis.Although NAFLD initially presents as benign fat accumulation,it may progress to steatosis,non-alcoholic steatohepatitis,cirrhosis,and hepatocellular carcinoma.Mesenchymal stem cells(MSCs)are recognized for their intrinsic self-renewal,superior biocompatibility,and minimal immunogenicity,positioning them as a therapeutic innovation for liver diseases.Therefore,this review aims to elucidate the potential roles of MSCs in alleviating the progression of NAFLD by alteration of underlying molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.The insights are expected to provide further understanding of the potential of MSCs in NAFLD therapeutics,and support the development of MSC-based therapy in the treatment of NAFLD. 展开更多
关键词 Non-alcoholic induced fatty liver disease mesenchymal stem cells Lipid accumulation INFLAMMATION Oxidative stress Endoplasmic reticulum stress fibrosis
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Neural differentiation of human Wharton's jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats 被引量:7
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作者 Lei Zhang Lin-mei Wang +10 位作者 Wei-wei Chen Zhi Ma Xiao Han Cheng-ming Liu Xiang Cheng Wei Shi Jing-jing Guo Jian-bing Qin Xiao-qing Yang Guo-hua Jin Xin-hua Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第7期1103-1110,共8页
Human Wharton's jelly-derived mesenchymal stem cells(h WJ-MSCs)have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their appli... Human Wharton's jelly-derived mesenchymal stem cells(h WJ-MSCs)have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior. 展开更多
关键词 nerve regeneration human Wharton's jelly-derived mesenchymal stem cells ischemic stroke cell transplantation middle cerebral arteryocclusion neural differentiation neurological function neural regeneration
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Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia 被引量:17
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作者 Lu Debin Jiang Youzhao Liang Ziwen Li Xiaoyan Zhang Zhonghui Chen Bing 《Journal of Medical Colleges of PLA(China)》 CAS 2008年第2期106-115,共10页
Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ... Objective: To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods: Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results: At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group (1 5 of 18, 83.33%) was significantly higher than that of the control group (9 of 20, 45.00%, P=0.012).The mean of resting ankle-brachial index (ABI) in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 (P〈0.001). Magnetic resonance angiography (MRA) demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients (11 of 15) than in control patients (2 of 14, P=0.001). Lower limb amputation rate was significantly lower in transplanted group than in the control group (P=0.040). No adverse effects was observed in transplanted group. Conclusion: These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients. 展开更多
关键词 Autologous transplantation mesenchymal stem cells Critical limb ischemia DIABETES
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Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation 被引量:12
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作者 Wen Zhang Zhong-Yang Shen +4 位作者 Hong-Li Song Yang Yang Ben-Juan Wu Nan-Nan Fu Tao Liu 《World Journal of Gastroenterology》 SCIE CAS 2014年第23期7442-7451,共10页
AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.
关键词 Bone marrow mesenchymal stem cells Small intestinal transplantation Intestinal mucosal barrier OCCLUDIN Zona occludens-1
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Umbilical Cord Blood-derived Mesenchymal Stem Cells Ameliorate Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation through Multiple Immunoregulations 被引量:5
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作者 吴秋玲 刘小云 +6 位作者 聂第敏 朱夏夏 方峻 游泳 仲照东 夏凌辉 洪梅 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2015年第4期477-484,共8页
Summary: Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate... Summary: Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^+, CD3+CD4^+ and CD3+CD8^+ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^+ and CD8^+ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations. 展开更多
关键词 graft-versus-host disease mesenchymal stem cells hematopoietic stem cell transplantation IMMUNOREGULATION
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Mesenchymal stem cells: A promising therapeutic avenue for nonalcoholic fatty liver disease
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作者 Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng 《World Journal of Stem Cells》 SCIE 2024年第8期780-783,共4页
Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and obesity.On the basis of the insights provided by Jiang et al,this editorial presents an explor... Non-alcoholic fatty liver disease(NAFLD)is a pressing global health concern that is associated with metabolic syndrome and obesity.On the basis of the insights provided by Jiang et al,this editorial presents an exploration of the potential of mesenchymal stem cells(MSCs)for NAFLD treatment.MSCs have numerous desirable characteristics,including immunomodulation,anti-inflammatory pro-perties,and tissue regeneration promotion,rendering them attractive candidates for NAFLD treatment.Recent preclinical and early clinical studies have high-lighted the efficacy of MSCs in improving liver function and reducing disease severity in NAFLD models.However,MSC heterogeneity,long-term safety concerns,and unoptimized therapeutic protocols remain substantial challenges.Addressing these challenges through standardized protocols and rigorous clinical trials is essential to the safe and successful application of MSCs in NAFLD mana-gement.Continued research into MSC mechanisms and therapeutic optimization is required to improve treatments for NAFLD and related liver diseases. 展开更多
关键词 mesenchymal stem cells Non-alcoholic fatty liver disease Therapeutic potential liver fibrosis Regenerative medicine stem cell therapy INFLAMMATION Clinical trials
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Mechanism of mesenchymal stem cells in liver regeneration:Insights and future directions
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作者 Yu-Xin Jin Hang-Qi Hu +4 位作者 Jia-Cheng Zhang Xi-Yan Xin Yu-Tian Zhu Yang Ye Dong Li 《World Journal of Stem Cells》 SCIE 2024年第9期842-845,共4页
Mesenchymal stem cells(MSCs)are a prevalent source for stem cell therapy and play a crucial role in modulating both innate and adaptive immune responses.Non-alcoholic fatty liver disease(NAFLD)is characterized by the ... Mesenchymal stem cells(MSCs)are a prevalent source for stem cell therapy and play a crucial role in modulating both innate and adaptive immune responses.Non-alcoholic fatty liver disease(NAFLD)is characterized by the accumulation of triglycerides in liver cells and involves immune system activation,leading to histological changes,tissue damage,and clinical symptoms.A recent publication by Jiang et al,highlighted the potential of MSCs to mitigate in NAFLD progression by targeting various molecular pathways,including glycolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and fibrosis.In this editorial,we comment on their research and discuss the efficacy of MSC therapy in treating NAFLD. 展开更多
关键词 mesenchymal stem cells liver regeneration Non-alcoholic fatty liver disease Immune cells Therapeutic strategy
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Use of mesenchymal stem cells to treat liver fibrosis:Current situation and future prospects 被引量:24
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作者 Silvia Berardis Prenali Dwisthi Sattwika +1 位作者 Mustapha Najimi Etienne Marc Sokal 《World Journal of Gastroenterology》 SCIE CAS 2015年第3期742-758,共17页
Progressive liver fibrosis is a major health issue for which no effective treatment is available,leading to cirrhosis and orthotopic liver transplantation.However,organ shortage is a reality.Hence,there is an urgent n... Progressive liver fibrosis is a major health issue for which no effective treatment is available,leading to cirrhosis and orthotopic liver transplantation.However,organ shortage is a reality.Hence,there is an urgent need to find alternative therapeutic strategies.Cellbased therapy using mesenchymal stem cells(MSCs) may represent an attractive therapeutic option,based ontheir immunomodulatory properties,their potential to differentiate into hepatocytes,allowing the replacement of damaged hepatocytes,their potential to promote residual hepatocytes regeneration and their capacity to inhibit hepatic stellate cell activation or induce their apoptosis,particularly via paracrine mechanisms.The current review will highlight recent findings regarding the input of MSC-based therapy for the treatment of liver fibrosis,from in vitro studies to pre-clinical and clinical trials.Several studies have shown the ability of MSCs to reduce liver fibrosis and improve liver function.However,despite these promising results,some limitations need to be considered.Future prospects will also be discussed in this review. 展开更多
关键词 liver fibrosis CIRRHOSIS mesenchymal stem cells Ce
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Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats 被引量:20
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作者 Ning-Li Chai Xiao-Bin Zhang +2 位作者 Si-Wen Chen Ke-Xing Fan En-Qiang Linghu 《World Journal of Gastroenterology》 SCIE CAS 2016年第26期6036-6048,共13页
AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with li... AIM: To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells(UC-MSCs) transplantation in the treatment of liver fibrosis.METHODS: Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine(DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin(IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells(KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were cocultured with KCs in vitro to assess the effects of UCMSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UCMSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.RESULTS: UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the coculture system resulted in decreased KC mobilization.CONCLUSION: UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN. 展开更多
关键词 liver fibrosis mesenchymal stem cells KUPFFER cells INTERLEUKIN-4 DIMETHYLNITROSAMINE DMN
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Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators
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作者 Ying Gao Mei-Fang Liu +5 位作者 Yang Li Xi Liu Yu-Jie Cao Qian-Fa Long Jun Yu Jian-Ying Li 《World Journal of Stem Cells》 SCIE 2024年第6期670-689,共20页
BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung failure.Stem cell therapy and mes... BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung failure.Stem cell therapy and mesenchymal stem cells-extracellular vesicles(MSC-EVs)offer new hope for PF treatment.AIM To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis,oxidative stress,and immune inflammation in A549 cells and bleomycin(BLM)-induced mouse model.METHODS The effect of MSC-EVs on A549 cells was assessed by fibrosis markers[collagen I andα-smooth muscle actin(α-SMA),oxidative stress regulators[nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1),and inflammatory regu-lators[nuclear factor-kappaB(NF-κB)p65,interleukin(IL)-1β,and IL-2].Similarly,they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV transfection.MSC-EVs ion PF mice were detected by pathological staining and western blot.Single-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in mice.RESULTS Transforming growth factor(TGF)-β1 enhanced fibrosis in A549 cells,significantly increasing collagen I andα-SMA levels.Notably,treatment with MSC-EVs demonstrated a remarkable alleviation of these effects.Similarly,the expression of oxidative stress regulators,such as Nrf2 and HO-1,along with inflammatory regulators,including NF-κB p65 and IL-1β,were mitigated by MSC-EV treatment.Furthermore,in a parallel manner,MSC-EVs exhibited a downregulatory impact on collagen deposition,oxidative stress injuries,and inflammatory-related cytokines in the lungs of mice with PF.Additionally,the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory response.The findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes,oxidative stress,and inflammatory responses associated with PF.CONCLUSION MSC-EVs could ameliorate fibrosis in vitro and in vivo by downregulating collagen deposition,oxidative stress,and immune-inflammatory responses. 展开更多
关键词 mesenchymal stem cells Extracellular vesicles Pulmonary fibrosis Oxidative stress response Epithelial-mesenchymal transition
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Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor
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作者 Qi-Hong Chen Ying Zhang +4 位作者 Xue Gu Peng-Lei Yang Jun Yuan Li-Na Yu Jian-Mei Chen 《World Journal of Stem Cells》 SCIE 2024年第8期811-823,共13页
BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to ex... BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer. 展开更多
关键词 Microvesicles derived from mesenchymal stem cells Acute respiratory distress syndrome Pulmonary fibrosis Hepatocyte growth factor mesenchymal stromal cells
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Enhancing the functionality of mesenchymal stem cells:An attractive treatment strategy for metabolic dysfunction-associated steatotic liver disease?
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作者 Xiao-Qian Shan Lan Zhao 《World Journal of Stem Cells》 SCIE 2024年第10期854-859,共6页
The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscori... The intrinsic heterogeneity of metabolic dysfunction-associated fatty liver disease(MASLD)and the intricate pathogenesis have impeded the advancement and clinical implementation of therapeutic interventions,underscoring the critical demand for novel treatments.A recent publication by Li et al proposes mesenchymal stem cells as promising effectors for the treatment of MASLD.This editorial is a continuum of the article published by Jiang et al which focuses on the significance of strategies to enhance the functionality of mesenchymal stem cells to improve efficacy in curing MASLD,including physical pretreatment,drug or chemical pretreatment,pretreatment with bioactive substances,and genetic engineering. 展开更多
关键词 Metabolic dysfunction-associated fatty liver disease mesenchymal stem cells Preprocess Cell survival Therapeutic strategy
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