肠促胰素是肠道细胞受食物刺激分泌并释放入血,包括胰高糖素样多肽1(glucagon like peptide-1,GLP-1)、葡萄糖依赖性促胰岛素多肽(glucose-dependent insulintropic polypeptide)等,能促进胰岛素分泌并调节血糖.GLP-1为小肠L细胞分泌,...肠促胰素是肠道细胞受食物刺激分泌并释放入血,包括胰高糖素样多肽1(glucagon like peptide-1,GLP-1)、葡萄糖依赖性促胰岛素多肽(glucose-dependent insulintropic polypeptide)等,能促进胰岛素分泌并调节血糖.GLP-1为小肠L细胞分泌,并通过特异性的GLP-1受体(glucagon like peptide-1receptor,GLP-1R)介导发挥生物学作用.而GLP-1R广泛分布于胰腺及胰腺外组织中包括中枢神经系统、胃肠道系统、心血管系统、肺、肾等组织器官.近年来,GLP-1类药物除了用于糖尿病患者的降糖治疗,因其在保护b细胞,降低体质量,改善内皮细胞功能,预防老年性痴呆均有一定的作用,而备受关注.本文将从GLP-1的合成分泌、对味觉、阿茨海默病的影响、与其他胃肠道激素关系对其进行阐述,为GLP-1更广泛的用于临床和未来的研发提供参考.展开更多
The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model...The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.展开更多
BACKGROUND Lymphedema is a chronic,debilitating and incurable disease that affects 0.13%-2%of the global population.Emerging evidence indicates that adipose-derived stem cells(ADSCs)might serve as suitable seed cells ...BACKGROUND Lymphedema is a chronic,debilitating and incurable disease that affects 0.13%-2%of the global population.Emerging evidence indicates that adipose-derived stem cells(ADSCs)might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy.AIM To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials.METHODS A systematic search was performed on four databases-PubMed,Clinicaltrials.gov,the evidence-based Cochrane Library,and OVID-using the following search string:(“lymphedema”or“lymphoedema”or“lymphangiogenesis”)and(“adipose-derived stem cells”or“adipose-derived stromal cells”or“adipose-derived regenerative cells”).A manual search was performed by skimming the references of relevant studies.Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included.RESULTS A total of eight research articles published before November 2019 were included for this analysis.Five articles focused on animal studies and another three focused on clinical trials.ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies.The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy.Three sequential clinical trials were conducted on breast cancer-related lymphedema patients,and all showed favorable results.CONCLUSION ADSC-based therapy is a promising option for treating lymphedema.Large-scale,multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,...BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.展开更多
Background:Researchers have explored the use of adipose-derived stem cells(ASCs)as a cellbased therapy to cover wounds in burn patients;however,underlying mechanistic aspects are not completely understood.We hypothesi...Background:Researchers have explored the use of adipose-derived stem cells(ASCs)as a cellbased therapy to cover wounds in burn patients;however,underlying mechanistic aspects are not completely understood.We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways.Methods:To test the hypothesis,we used an ovine burn model.A 5 cm^(2) full thickness burn wound was induced on each side of the dorsum.After 24 hours,the burned skin was excised and a 2 cm^(2) patch of autologous donor skin was grafted.The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment(phosphate-buffered saline[PBS]).Effects of ASCs culture media was also compared to those of PBS.Wound healing was assessed at one and two weeks following the application of ASCs.Allogeneic ASCs were isolated,cultured and characterized from non-injured healthy sheep.The identity of the ASCs was confirmed by flow cytometry analysis,differentiation into multiple lineages and gene expression via real-time polymerase chain reaction.Wound blood flow,epithelialization,graft size and take and the expression of vascular endothelial growth factor(VEGF)were determined via enzyme-linked immunosorbent assay and Western blot.Results:Treatment with ASCs accelerated the patch graft growth compared to the control(p<0.05).Topical application of ASCs significantly increased wound blood flow(p<0.05).Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control(p<0.05).Conclusions:ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.展开更多
BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering...BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering,decreases in the late stage of induced chondrogenic differentiation in vitro,which seriously limits research on ADSCs and their application.AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro,and optimize the existing chondrogenic induction protocol.METHODS Tumor necrosis factor-alpha(TNF-α)inhibitor was added to chondrogenic culture medium,and then Western blotting,enzyme linked immunosorbent assay,immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B(NF-κB)signaling pathway.RESULTS In this study,we found that the levels of TNF-αand matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs.TNF-αthen bound to its receptor and activated the NF-κB pathway,leading to a decrease in cartilage matrix synthesis and secretion.Blocking TNF-αwith its inhibitors etanercept(1μg/mL)or infliximab(10μg/mL)significantly restored matrix formation.CONCLUSION Therefore,this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs,and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.展开更多
AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(con...AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally(100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis(macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor(TNF)-α in liver(156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced(23.2 ± 6.9 and 12.1 ± 1.6 U/L for nontreated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α(106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6(340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin(8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1(600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non展开更多
This study was designed to investigate the effects of local delivery of adipose-derived stem cells （ADSCs） transfected with transcription factor osterix （OSX） on bone formation during distraction osteogenesis. New...This study was designed to investigate the effects of local delivery of adipose-derived stem cells （ADSCs） transfected with transcription factor osterix （OSX） on bone formation during distraction osteogenesis. New Zealand white rabbits （n=54） were randomly divided into three groups （18 rabbits per group）. A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the dght mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density （BMD）. Three parameters were measured, namely, the thickness of new trabeculae （TNT）, and the volumes of the newly generated cortical bone （NBV1） and the cancellous bone （NBV2） of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo.展开更多
文摘肠促胰素是肠道细胞受食物刺激分泌并释放入血,包括胰高糖素样多肽1(glucagon like peptide-1,GLP-1)、葡萄糖依赖性促胰岛素多肽(glucose-dependent insulintropic polypeptide)等,能促进胰岛素分泌并调节血糖.GLP-1为小肠L细胞分泌,并通过特异性的GLP-1受体(glucagon like peptide-1receptor,GLP-1R)介导发挥生物学作用.而GLP-1R广泛分布于胰腺及胰腺外组织中包括中枢神经系统、胃肠道系统、心血管系统、肺、肾等组织器官.近年来,GLP-1类药物除了用于糖尿病患者的降糖治疗,因其在保护b细胞,降低体质量,改善内皮细胞功能,预防老年性痴呆均有一定的作用,而备受关注.本文将从GLP-1的合成分泌、对味觉、阿茨海默病的影响、与其他胃肠道激素关系对其进行阐述,为GLP-1更广泛的用于临床和未来的研发提供参考.
基金the National Basic Research Program of China(973Program),No.2007CB512705the General Program for Youths of the National Natural Science Foundation of China,No.30801464
文摘The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein. Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.
文摘BACKGROUND Lymphedema is a chronic,debilitating and incurable disease that affects 0.13%-2%of the global population.Emerging evidence indicates that adipose-derived stem cells(ADSCs)might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy.AIM To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials.METHODS A systematic search was performed on four databases-PubMed,Clinicaltrials.gov,the evidence-based Cochrane Library,and OVID-using the following search string:(“lymphedema”or“lymphoedema”or“lymphangiogenesis”)and(“adipose-derived stem cells”or“adipose-derived stromal cells”or“adipose-derived regenerative cells”).A manual search was performed by skimming the references of relevant studies.Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included.RESULTS A total of eight research articles published before November 2019 were included for this analysis.Five articles focused on animal studies and another three focused on clinical trials.ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies.The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy.Three sequential clinical trials were conducted on breast cancer-related lymphedema patients,and all showed favorable results.CONCLUSION ADSC-based therapy is a promising option for treating lymphedema.Large-scale,multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.
基金Supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT),No.NRF-2021R1F1A1064566.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.
基金This project was supported by grants from:the Shriners Hospitals for Children 84050 to PE and 84202 to AEAthe National Institutes of Health to DNH(R01-GM56687,P50-GM-60338)and to CCF(R01-GM-112936)the Anderson Foundation and the Gillson Longebaugh Foundation to DNH and CCF.The project was conducted with the support of the University of Texas Medical Branch’s Institute for Translational Sciences,supported in part by a Clinical and Translational Science Award(UL1TR000071)from the National Center for Advancing Translational Sciences(NIH).
文摘Background:Researchers have explored the use of adipose-derived stem cells(ASCs)as a cellbased therapy to cover wounds in burn patients;however,underlying mechanistic aspects are not completely understood.We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways.Methods:To test the hypothesis,we used an ovine burn model.A 5 cm^(2) full thickness burn wound was induced on each side of the dorsum.After 24 hours,the burned skin was excised and a 2 cm^(2) patch of autologous donor skin was grafted.The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment(phosphate-buffered saline[PBS]).Effects of ASCs culture media was also compared to those of PBS.Wound healing was assessed at one and two weeks following the application of ASCs.Allogeneic ASCs were isolated,cultured and characterized from non-injured healthy sheep.The identity of the ASCs was confirmed by flow cytometry analysis,differentiation into multiple lineages and gene expression via real-time polymerase chain reaction.Wound blood flow,epithelialization,graft size and take and the expression of vascular endothelial growth factor(VEGF)were determined via enzyme-linked immunosorbent assay and Western blot.Results:Treatment with ASCs accelerated the patch graft growth compared to the control(p<0.05).Topical application of ASCs significantly increased wound blood flow(p<0.05).Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control(p<0.05).Conclusions:ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.
基金Thanks to Peking University Hong Kong University of Science and Technology Medical Center for providing the research instruments and workplace.
文摘BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering,decreases in the late stage of induced chondrogenic differentiation in vitro,which seriously limits research on ADSCs and their application.AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro,and optimize the existing chondrogenic induction protocol.METHODS Tumor necrosis factor-alpha(TNF-α)inhibitor was added to chondrogenic culture medium,and then Western blotting,enzyme linked immunosorbent assay,immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B(NF-κB)signaling pathway.RESULTS In this study,we found that the levels of TNF-αand matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs.TNF-αthen bound to its receptor and activated the NF-κB pathway,leading to a decrease in cartilage matrix synthesis and secretion.Blocking TNF-αwith its inhibitors etanercept(1μg/mL)or infliximab(10μg/mL)significantly restored matrix formation.CONCLUSION Therefore,this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs,and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.
基金Supported by The Fundacao de Amparoà Pesquisa do Estado de Sao Paulo,No.FAPESP 2011/00518-4
文摘AIM:To study pentoxifylline effects in liver and adipose tissue inflammation in obese mice induced by high-fat diet(HFD).METHODS: Male swiss mice(6-wk old) were fed a highfat diet(HFD; 60% kcal from fat) or AIN-93(control diet; 15% kcal from fat) for 12 wk and received pentoxifylline intraperitoneally(100 mg/kg per day) for the last 14 d. Glucose homeostasis was evaluated by measurements of basal glucose blood levels and insulin tolerance test two days before the end of the protocol. Final body weight was assessed. Epididymal adipose tissue was collected and weighted for adiposity evaluation. Liver and adipose tissue biopsies were homogenized in solubilization buffer and cytokines were measured in supernatant by enzyme immunoassay or multiplex kit, respectively. Hepatic histopathologic analyses were performed in sections of paraformaldehyde-fixed, paraffin-embedded liver specimens stained with hematoxylin-eosin by an independent pathologist. Steatosis(macrovesicular and microvesicular), ballooning degeneration and inflammation were histopathologically determined. Triglycerides measurements were performed after lipid extraction in liver tissue. RESULTS: Pentoxifylline treatment reduced microsteatosis and tumor necrosis factor(TNF)-α in liver(156.3 ± 17.2 and 62.6 ± 7.6 pg/mL of TNF-α for non-treated and treated obese mice, respectively; P < 0.05). Serum aspartate aminotransferase levels were also reduced(23.2 ± 6.9 and 12.1 ± 1.6 U/L for nontreated and treated obese mice, respectively; P < 0.05) but had no effect on glucose homeostasis. In obese adipose tissue, pentoxifylline reduced TNF-α(106.1 ± 17.6 and 51.1 ± 9.6 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) and interleukin-6(340.8 ± 51.3 and 166.6 ± 22.5 pg/mL for non-treated and treated obese mice, respectively; P < 0.05) levels; however, leptin(8.1 ± 0.7 and 23.1 ± 2.9 ng/mL for non-treated and treated lean mice, respectively; P < 0.05) and plasminogen activator inhibitor-1(600.2 ± 32.3 and 1508.6 ± 210.4 pg/mL for non
基金Project supported by the Seed Fund of the Second Hospital of Shandong University (No.S2013010024),China
文摘This study was designed to investigate the effects of local delivery of adipose-derived stem cells （ADSCs） transfected with transcription factor osterix （OSX） on bone formation during distraction osteogenesis. New Zealand white rabbits （n=54） were randomly divided into three groups （18 rabbits per group）. A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the dght mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density （BMD）. Three parameters were measured, namely, the thickness of new trabeculae （TNT）, and the volumes of the newly generated cortical bone （NBV1） and the cancellous bone （NBV2） of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo.
