Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Differentiate Into Insulin-Producing Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4578-4578
Author(s):  
Lian Ma ◽  
Hongwu Wang ◽  
Hongyan He ◽  
Limin Lin ◽  
Weizhong Li ◽  
...  

Abstract Abstract 4578 Introduction Islet transplantation is an effective way of reversing type 1 diabetes. However, islet transplantation has been hampered by problems, such as immune rejection, and the scarcity of donor islets. Human Umbilical Cord Wharton's Jelly-derived Mesenchymal Stem Cells (huMSCs), which can be differentiated into insulin-producing cells could provide a source of cells for transplant. Methods Vitro Research We isolated and cultured huMSCs, and induced huMSCs differentiated into insulin-producing cells in the condition of islet cells grows. The morphology of huMSCs after induction were monitored by under inversion phase contrast microscope?GImmunocytochemical methods were used to detect the insulin and glucagon protein, and reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect Human insulin gene and PDX-1 gene. Dithizon-stained was used to detect zinc hydronium and radio-immunity was used to detect insulin level of culture supernatant.Vivo Research huMSCs were transplanted into the body of diabetic rats through vena caudalis, and then we observed the change of blood glucose?Abody weight ?Aserum insulin levels and survival ratio in STZ-induced diabetic rats. We detected human insulin by immunohistochemistry and RT-PCR. HE stain was used to detect the morphological changes of rat's pancreatic island. Results Vitro Research The morphology of huMSCs under medicine induction gradually changed from fibroblast to round and some of then had the tend of forming clusters.?GThe result of immunocytochemical showed that the expression of human insulin and glucagon was positive after treatment with medicine?GhuMSCs induced by medicine can express insulin and PDX-1 gene by RT-PCR?GDithizon stain show that the cytoplasm of huMSCs after induction were stained in Brownish red color?Gthe results of radio-immunity manifested that the insulin quantity secreted by medicine induction were significant differences compared with control group(t??6.183,P<0.05). Vivo Research When transplanted into Streptozotocin(STZ)-treated diabetics rats, huMSCs can decreased blood glucose, increased body weight and survival ratio in diabetic rats?GAfter being transplanted for one month, we discovered that it can be planted into rat's pancreas and liver by Hoechst33258?Gimmunohistochemistry and RT-PCR show that the pancreas of rat can express human insulin?Gthe morphology of rats' pancreatic island was repaired obviously if compared with diabetic rats before the transplantation through HE-stain. Conclusion huMSCs can be differentiated into insulin-producing cells in vitro or in vivo. Therefore, huMSCs have the potential to become an excellent candidate in β cell replacement therapy of diabetes. Disclosures: No relevant conflicts of interest to declare.

2017 ◽  
Vol 13 (4) ◽  
pp. 1456-1464 ◽  
Author(s):  
Xiao-Fei Yang ◽  
Tao Chen ◽  
Li-Wei Ren ◽  
Lu Yang ◽  
Hui Qi ◽  
...  

2008 ◽  
Vol 31 (6) ◽  
pp. 328 ◽  
Author(s):  
Qing-Yu Dong ◽  
Li Chen ◽  
Guan-Qi Gao ◽  
Lei Wang ◽  
Jun Song ◽  
...  

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stroma cells which can provide a potential therapy for diabetes mellitus. But the mechanism is still controversial. Also, the status of BM-MSCs under hyperglycemia is not known. In the present study, we investigated the status of BM-MSCs in experimental-diabetic rat and demonstrated the rescue of experimental diabetes by diabetic MSCs transplantation. Methods: BM-MSCs were cultured and the potential of multiple-differentiation was identified through induction into osteoblasts. MSCs of passage 3 were used for the following experiment. The MSCs were labeled with 5-bromo-2?-deoxyuridine (BrdU). Diabetes in rats was induced by STZ injection. The rats were divided into three groups: normal control group (no DM, rats treated with saline through tail vein, n=10); DM control group (DM, no transplantation of MSCs, n=20); experimental group (DM and transplantation of MSCs, n=20). Body weight and blood glucose of the rats were monitored during the experiment after transplantation of MSCs. Paraffin sections of pancreas were obtained from rats of each group. Immuno-histochemistry analysis and double immunofluorescence were used to detect the BM-MSCs in the pancreatic tissue and their differentiating state. Results: MSCs were 89.5% labeled by BrdU and DAPI, which was green/blue double stained under fluorescent microscopy. Transplantation of diabetic MSCs resulted in a reduction of hyperglycemia on day 45 in experimental diabetic rats compared with control rats (17.7 mM ±3.9 vs 27.8 mM ± 2.1, P < 0.05), There was also a difference between MSC-treated experimental diabetic rats and control rats in body weight (232.7 g ±19.7 vs 133.3g ±13.1, P < 0.05). Histological and morphometric analysis of the pancreas of experimental diabetic rats showed the presence and differentiation of transplanted MSCs into insulin-producing cells which evidenced by double-staining of anti-BrdU and insulin. Also, there were many small islets throughout the sections. Their mean area and diameter analysis revealed that they were smaller thancontrol islets (1835.7 ± 175.8 µm2 vs 13257.2 ± 1457.6 µm2; 43.5 ± 3.7 µm vs 119.9 ± 5.8 µm, respectively, P < 0.05). Conclusion: Allogeneic MSCs transplantation can reduce blood glucose level in recipient rats. A relatively small quantity of transplanted diabetic MSCs survive and transdifferentiate into insulin-producing cells in the pancreas of recipient rats. Upon transplantation these cells initiate endogenous pancreatic regeneration by neogenesis of islet of recipient origin. The present study demonstrates that diabetic MSCs retains its stemness and potential to induce pancreatic regeneration on transplantation.


2021 ◽  
Author(s):  
Tianqin Xie ◽  
Qiming Huang ◽  
Qiulang Huang ◽  
Haixia Zeng ◽  
Jianping Liu

Abstract ObjectiveIn recent years, cell therapy has become a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cells (MSCs) participate in such treatment has not been clarified. MethodsIn this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSCs (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). ResultsWe found that the number of differentially expressed lncRNAs and mRNAs showed a decreasing trend during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signaling pathway, MAPK signaling pathway, HIPPO signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA: CTBP1-AS2 with the PROX1, and the lncRNAs AC009014.3 and GS1-72M22.1 with the mRNA JARID2 was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs :XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells.ConclusionThis research revealed that HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signaling pathways. The lncRNAs: AC009014.3,Gs1-72m21.1 and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalog for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.


2021 ◽  
Author(s):  
Yan Fu ◽  
Zhao-Hui Gu ◽  
Yue-Ling Zhang ◽  
Xiao-Ying Wen ◽  
Na Yang

Abstract Diabetic retinopathy (DR) is a highly specific condition affecting the microvasculature that is the leading cause of visual impairment in working-age people in developed countries. The ability of intravitreal administration of mesenchymal stem cells (MSCs) to repair the retinal vasculature and neurons of the inner retina in DR has been explored. It was recently revealed that exosomes are primarily responsible for the therapeutic effects of MSCs; therefore, intravitreal injection of these vesicles appears to be a better option for treatment of retinal injury, and there is evidence that hypoxic conditions can promote exosome release from MSCs. Here we investigated the effect of intravitreal injection of hypoxia-induced human umbilical cord mesenchymal stem cell exosomes (hypo-hucMSC-Exs) on the retinal microvasculature in rats with DR. We also assessed whether hypo-hucMSC-Exs exhibited greater effects on DR than exosomes from human umbilical cord mesenchymal stem cells not exposed to hypoxia (hucMSC-Exs). Exosomes were isolated from MSCs cultured under normoxic and hypoxic culture conditions. Transmission electron microscope, nanoparticle tracking, and western blot analyses were applied to characterize hucMSC-Exs. Streptozotocin (STZ)-induced diabetic rats were used as a model for DR. Fundus fluorescein angiography (FFA) was conducted to evaluate retinal microvasculature changes in vivo at 4, 8, and 12 weeks following intravitreal injection of exosomes. No significant changes were observed in the control rats without DR receiving intravitreal phosphate-buffered saline (PBS) injection throughout the study. Control model rats receiving PBS injections developed DR characterized by retinal microvascular changes, including tortuous vessels, massive microaneurysms, and late leakage of fluorescein dye was, which were visualized using FFA. These changes were ameliorated in diabetic rats treated with hucMSC-Exs. Further, injection of hypo-hucMSC-Exs remarkably reduced the extent of microvasculature lesions compared with hucMSC-Exs. These findings suggest that intravitreal injection of hucMSC-Exs can prevent diabetes-induced microvasculature lesions and that hypo-hucMSC-Exs can enhance this effect and have potential for application in DR prevention and treatment.


Sign in / Sign up

Export Citation Format

Share Document