Insulin-producing cell clusters derived from human gingival mesenchymal stem cells as a model for diabetes research

Kharat, Avinash; Sanap, Avinash; Kheur, Supriya; Shekatkar, Madhura; Bhonde, Ramesh

doi:10.1007/s11033-022-08008-6

Cited by 6 publications

(3 citation statements)

References 42 publications

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“…Therefore, except if needed for anesthesia, insulin was not used to alter blood glucose levels in this study. Non-human primates are more closely related to humans than rodents, and transplantation of human-derived IPCs into non-human primates can achieve short-term efficacy without the use of immune induction or immunosuppressive agents, 1,23 so this study also omitted immune intervention. In the early stage of clinical islet transplantation, instant blood-mediated inflammatory reaction (IBMIR)mediated massive insulin release occurs, which can lead to hypoglycemic shock.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of insulin‐producing cells derived from human MSCs to treat diabetes in a non‐human primate model

et al. 2023

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BackgroundIslet cell transplantation is an emerging therapy in the treatment of diabetes mellitus. Differentiation of islet cells from mesenchymal stem cells (MSCs) is a potential solution to the challenge of insufficient donor sources. This study investigated whether human umbilical cord‐derived MSCs could effectively differentiate into insulin‐producing cells (IPCs) and evaluated the therapeutic efficacy of IPCs in treating diabetes.MethodsIPCs were induced from MSCs by a two‐step protocol. IPC expression products were evaluated by western blot and real‐time PCR. IPC insulin secretion was evaluated by ELISA. The viability of IPCs was measured by FDA/PI and dithizone staining. The non‐human primate tree shrew was used as a diabetes model. After a single STZ induction into a diabetes model, a single intraportal transplantation of IPCs, MSCs, or normal saline was performed (n = 6 per group). Blood glucose was monitored for 3 weeks, then the animals were euthanized and the distribution of IPCs in the liver was examined pathologically.ResultsAfter about 3 weeks of in vitro induction, IPCs formed microspheres of 100–200 μm, with >95% viable cells that were dithizone stain positive. IPCs expressed islet‐related genes and proteins and secreted high levels of insulin whether stimulated by low or high levels of glucose. After transplantation of IPCs into diabetic tree shrews, blood glucose levels decreased rapidly to near normal and were significantly lower than the MSC or saline groups for 3 weeks thereafter.ConclusionWe present the novel discovery that IPCs derived from human umbilical cord MSCs exert a therapeutic effect in a non‐human primate model of diabetes. This study provides a preliminary experimental basis for the use of autologous MSC‐derived IPCs in the treatment of human diabetes.

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Section: Discussionmentioning

confidence: 99%

Transplantation of insulin‐producing cells derived from human MSCs to treat diabetes in a non‐human primate model

et al. 2023

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“…Human GMSCs have recently demonstrated the ability to differentiate into Insulin Producing Cell Clusters (IPCCs) and to express pancreatic markers such as insulin, pdx1, glucagon, GLUT4, and GLUT2 in vitro [ 95 ]. As a result, the GMSCs provide an attractive, approachable, and non-invasive model source for diabetes research as well as for autologous stem cells transplantation in type 1 diabetic patients without the requirement for immunosuppression.…”

Section: Translational Relevance Of Gingiva-derived Mesenchymal Proge...mentioning

confidence: 99%

Hiding in Plain Sight: Human Gingival Fibroblasts as an Essential, Yet Overlooked, Tool in Regenerative Medicine

Fadl

Leask

2023

Cells

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Adult human gingival fibroblasts (HGFs), the most abundant cells in the oral cavity, are essential for maintaining oral homeostasis. Compared with other tissues, adult oral mucosal wounds heal regeneratively, without scarring. Relative to fibroblasts from other locations, HGFs are relatively refractory to myofibroblast differentiation, immunomodulatory, highly regenerative, readily obtained via minimally invasive procedures, easily and rapidly expanded in vitro, and highly responsive to growth factors and cytokines. Consequently, HGFs might be a superior, yet perhaps underappreciated, source of adult mesenchymal progenitor cells to use in tissue engineering and regeneration applications, including the treatment of fibrotic auto-immune connective tissue diseases such as scleroderma. Herein, we highlight in vitro and translational studies that have investigated the regenerative and differentiation potential of HGFs, with the objective of outlining current limitations and inspiring future research that could facilitate translating the regenerative potential of HGFs into the clinic.

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“…Dithizone could cause the rupture of insulin-storing vesicles in pancreatic β-cells [71]. Currently, this substance is used to determine the purity of a sample of pancreatic islets before transplantation and/or to prove the presence of insulin cells [72].…”

Section: Chemical Modelsmentioning

confidence: 99%

Animal Models in Diabetic Research—History, Presence, and Future Perspectives

Pandey,

Chmelir,

Chottova Dvorakova

2023

Biomedicines

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Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as “organ-on-chip,” that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.

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Insulin-producing cell clusters derived from human gingival mesenchymal stem cells as a model for diabetes research

Cited by 6 publications

References 42 publications

Transplantation of insulin‐producing cells derived from human MSCs to treat diabetes in a non‐human primate model

Transplantation of insulin‐producing cells derived from human MSCs to treat diabetes in a non‐human primate model

Hiding in Plain Sight: Human Gingival Fibroblasts as an Essential, Yet Overlooked, Tool in Regenerative Medicine

Animal Models in Diabetic Research—History, Presence, and Future Perspectives

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