Impact of Insulin Producing Cells Derived from Adipose Tissue Mesenchymal Stem Cells on Testicular Dysfunction of Diabetic Rats

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.

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Intraportal injection of insulin-producing cells generated from human bone marrow mesenchymal stem cells decreases blood glucose level in diabetic rats

Endocrine Research ◽

10.3109/07435800.2013.797432 ◽

2013 ◽

Vol 39 (1) ◽

pp. 26-33 ◽

Cited By ~ 8

Author(s):

Pei-Jiun Tsai ◽

Hwai-Shi Wang ◽

Chi-Hung Lin ◽

Zen-Chung Weng ◽

Tien-Hua Chen ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

Diabetic Rats ◽

Human Bone ◽

Insulin Producing Cells ◽

Marrow Mesenchymal Stem Cells

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

Blood ◽

10.1182/blood.v114.22.4578.4578 ◽

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.

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From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells

BioMed Research International ◽

10.1155/2017/3854232 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Mahmoud M. Gabr ◽

Mahmoud M. Zakaria ◽

Ayman F. Refaie ◽

Engy A. Abdel-Rahman ◽

Asmaa M. Reda ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Regenerative Medicine ◽

C Peptide ◽

Metabolic Characteristics ◽

Insulin Producing Cells ◽

Glucose Challenge

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine.Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.

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

Journal of Cellular Physiology ◽

10.1002/jcp.27426 ◽

2018 ◽

Vol 234 (5) ◽

pp. 6801-6809 ◽

Cited By ~ 4

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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Deducing insulin producing cells in goat adipose tissue derived mesenchymal stem cells

10.21203/rs.3.rs-243143/v1 ◽

2021 ◽

Author(s):

Amit Dubey ◽

Hruda Nanda Malik ◽

Dinesh Kumar ◽

Sikander Saini ◽

Satish Kumar ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Regenerative Medicine ◽

Basic Mechanism ◽

Specific Protein ◽

Specific Gene ◽

Pancreatic Cells ◽

Insulin Producing Cells

Abstract Background: Mesenchymal stem cells (MSCs) is a new herald for regenerative medicine for control of incurable diseases in human and animals. Diabetes occurs when the blood glucose is high due to lack of insulin hormone secreted by the pancreatic cells. The global diabetes in 2019 is estimated 463 million people and rising to 578 million by 2030. Methods: Here we differentiated goat adipose tissue derived MSCs into insulin producing cells. To achieve this, the goat MSCs were cultured in serum-free DMEM/F12 medium containing glucose, nicotinamide, activin-A, exendin-4, pentagastrin, retinoic acid and mercaptoethanol for three weeks. The in vitro differentiation ADSCs into insulin-producing cells was confirmed by detecting the pancreatic endoderm specific markers i.e. Igf-1, Sst, Ngn3, Pdx-1, Isl-1, c-Kit, Thy-1, and Glut-2 in differentiating cells. Results: There was a significant increase in insulin specific gene expression with respect to duration of differentiation. Pancreatic insulin-producing cells were further characterized by immunolocalization of Pdx-1, insulin, and Islets-1 specific protein. The release of insulin in response to a glucose challenge was also evaluated. Conclusions: The study provides new opportunities for deciphering the basic mechanism of in vitro genesis of pancreatic cells and basic properties, availability, and abundance of ADSCs render them well-suited for applications in regenerative medicine.

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