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

Abstract

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.

Current state of stem cell research in non-human primates: an overview

“…From the eighth week, the average postprandial C-peptide level reached about 2 ng/mL−1, which is 5 times the peak obtained after portal vein infusion of hPSC-islets and is related to a 44 % reduction in glycated hemoglobin level at 12 weeks [ 82 ]. A recent study showed that insulin-producing cells (IPCs) differentiated from human MSCs and transplanted via the portal vein into a non-human primate tree shrew model of diabetes rapidly reduced blood glucose levels to near-normal levels and remained significantly lower than the MSC group or saline group over the subsequent 3 weeks [ 83 ]. The omentum is an attractive extrahepatic alternative site for clinical islet transplantation, researchers have explored a method to transplant allogeneic islets to the omentum, and in three types of diabetic NHPs, the omentum is bioengineered with plasma-thrombin biodegradable matrix.…”

Novel lipid mediator 7S,14R-docosahexaenoic acid: biogenesis and harnessing mesenchymal stem cells to ameliorate diabetic mellitus and retinal pericyte loss

“…Multiple differentiation capacity, paracrine functions, and immunomodulation action make the marrow mesenchymal stem cells (MSCs) a good candidate for prevention or cure of diabetic mellitus and complications ( Vija et al, 2009 ; Bernardi et al, 2012 ; Miklosz and Chabowski, 2023 ; Aglan et al, 2024 ). Transplantation of bone marrow–derived cells increased levels of serum insulin and reduced blood glucose levels in hyperglycemic mice with streptozotocin-induced pancreatic tissue damage, which improved the metabolic state and survival of recipients ( Hess et al, 2003 ; Zhoujun et al, 2023 ). Studies using rat MSCs ( Boumaza et al, 2009 ; Yousef et al, 2022 ) or human bone marrow–derived multipotent stromal cells ( Lee et al, 2006 ; Gabr et al, 2013 ; Carlsson et al, 2023 ) have shown similar results of enhanced insulin secretion and repair of pancreatic islets after streptozotocin treatment in rodents.…”

Islet Like Cells Induced from Umbilical Cord Mesenchymal Stem Cells with Neonatal Bovine Pancreatic Mesenchymal Exosomes for Treatment of Diabetes Mellitus

“…ation into a variety of functional cells, so UCMSC is an ideal cell for the treatment of diabetes [6][7][8]. UCMSC can be induced as insulin-secreting cells [9][10][11][12][13][14], but these studies reported that only animal models were tested at the cellular level, and not the sensitivity to sugar concentration and safety in humans at the cellular level.…”