scholarly journals Control of Hyperglycemia Using Differentiated and Undifferentiated Mesenchymal Stem Cells in Rats with Type 1 Diabetes

2020 ◽  
Vol 209 (1) ◽  
pp. 13-25
Author(s):  
Ehsan Aali ◽  
Zahra Madjd ◽  
Neda Tekiyehmaroof ◽  
Ali Mohammad Sharifi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immunohistochemical Analysis ◽  
Diabetic Rats ◽  
Insulin Levels ◽  
Insulin Producing Cells ◽  
Differentiation Protocol ◽  
Streptozotocin Induced Diabetes ◽  
Diabetic Individual

Due to their ability in self-renewing and differentiation into a wide variety of tissues, mesenchymal stem cells (MSCs) exhibit outstanding potential for regenerative medicine. This study was aimed at investigating different aspects of MSC therapy in controlling hyperglycemia in streptozotocin-induced diabetes rats. Using an islet cell differentiation protocol, bone marrow (BM) MSCs were differentiated into insulin-producing cells (IPCs). The differentiation process was evaluated by immunocytochemistry, reverse transcriptase PCR, and dithizone staining. Diabetic animals in 4 diabetic individual groups received normal saline, BM-MSCs, coadministration of BM-MSCs with supernatant, and IPCs. Blood glucose and insulin levels were monitored during the experiment. Immunohistochemical analysis of the pancreas was performed at the end of the experiment. Administration of BM-MSCs could not reverse glucose and insulin levels in experimental animals as efficiently as cotransplantation of BM-MSCs with supernatant. The effect of coadministration of BM-MSCs with supernatant and transplantation of IPCs on controlling hyperglycemia is comparable. Immunohistochemical analysis showed that number and size of islets per section were significantly increased in groups receiving IPCs and BM-MSC-supernatant compared to the MSC group of animals. In conclusion, coadministration of BM-MSCs with supernatant could be used as efficiently as IPC transplantation in controlling hyperglycemia in diabetic rats.

Differentiation of mesenchymal stem cells to insulin-producing cells and their impact on type 1 diabetic rats

2010 ◽  
Vol 66 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Zeinab Neshati ◽  
Maryam M. Matin ◽  
Ahmad Reza Bahrami ◽  
Ali Moghimi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Rats ◽  
Insulin Producing Cells

Insulin-Producing Cells Differentiated from Adipose Mesenchymal Stem Cells Neuroprotection Strategy in Diabetic Rats

Metabolism ◽  
2021 ◽  
Vol 116 ◽  
pp. 154658
Author(s):  
K.M. Wartchow ◽  
L. Rodrigues ◽  
N.G. Selistre ◽  
L. Lissner ◽  
A. Moreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Rats ◽  
Insulin Producing Cells ◽  
Adipose Mesenchymal Stem Cells

scholarly journals Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Guo Qing-Song ◽  
Zhu Ming-Yan ◽  
Wang Lei ◽  
Fan Xiang-Jun ◽  
Lu Yu-Hua ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Physiological Function ◽  
Insulin Biosynthesis ◽  
Insulin Producing Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Glucose Challenge ◽  
Streptozotocin Induced Diabetes ◽  
Treatment Of Diabetes

Aims. The goal of cell transcription for treatment of diabetes is to generate surrogateβ-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normalβ-cells.Methods. Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.Results. Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.Conclusions. These findings suggest major implications for cell replacement strategies in generation of surrogateβ-cells for the treatment of diabetes.

scholarly journals Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat

2008 ◽  
Vol 31 (6) ◽  
pp. 328 ◽  
Author(s):  
Qing-Yu Dong ◽  
Li Chen ◽  
Guan-Qi Gao ◽  
Lei Wang ◽  
Jun Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Pancreatic Regeneration ◽  
Insulin Producing Cells ◽  
The Status

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.

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 ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Umbilical Cord ◽  
Human Insulin ◽  
Diabetic Rats ◽  
Human Umbilical Cord ◽  
Survival Ratio ◽  
Rt Pcr ◽  
Insulin Producing Cells

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.

Differentiation of microfluidic-encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats

2018 ◽  
Vol 234 (5) ◽  
pp. 6801-6809 ◽  
Author(s):  
Ghasem Barati ◽  
Samad Nadri ◽  
Ramin Hajian ◽  
Ali Rahmani ◽  
Hossein Mostafavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Trabecular Meshwork ◽  
Diabetic Rats ◽  
Insulin Producing Cells
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