Protective Effect of Human Mesenchymal Stem Cells on the Survival of Pancreatic Islets

Abstract

Background and Objectives: Transplantation of pancreatic islets is an intriguing new therapeutic option to face the worldwide spread problem of Type-I diabetes. Currently, its clinical use is limited by several problems, mainly based on the high number of islets required to restore normoglycaemia and by the low survival of the transplanted tissue. A promising attempt to overcome the limits to such an approach was represented by the use of Mesenchymal Stem Cells (MSC). Despite the encouraging results obtained with murine-derived MSC, little is still known about their protective mechanisms. The aim of the present study was to verify the effectiveness, (besides murine MSC), of clinically relevant human-derived MSC (hMSC) on protecting pancreatic islets, thus also shedding light on the putative differences between MSC of different origin. Methods and Results: Threefold kinds of co-cultures were therefore in vitro set up (direct, indirect and mixed), to analyze the hMSC effect on pancreatic islet survival and function and to study the putative mechanisms involved. Although in a different way with respect to murine MSC, also human derived cells demonstrated to be effective on protecting pancreatic islet survival. This effect could be due to the release of some trophic factors, such as VEGF and Il-6, and by the reduction of inflammatory cytokine TNF-α. Conclusions: Therefore, hMSC confirmed their great clinical potential to improve the feasibility of pancreatic islet transplantation therapy against diabetes.

Microfluidically fabricated fibers containing pancreatic islets and mesenchymal stromal cells improve longevity and sustained normoglycemia in diabetic rats

“…However, the secretion of immunomodulatory cytokines by MSCs modulated the immune response and eventually the pericapsular fibrotic overgrowth and secretions of fibroblasts and macrophages [45]. Our study observed that the incorporation of MSCs reduced the secretion of TNF-α, a pro-inflammatory cytokine, which is in accordance with previous studies [44,46,47]. It was suggested that the incorporation of MSCs led to the upregulation of IL-10 and granulocyte-colony stimulating factor, which play an inhibitory role in the production of TNF-α [45].…”

“…Their results showed that indirect culture led to the loss of morphology in islets. However, in the direct co-culture, MSCs coated almost the entire surface of the islets, which preserved the rounded morphology of the islets [44]. Our previous study also showed that co-transplantation of islets and MSCs improved the survival and functionality of the islets.…”

A New Islet Transplantation Method Combining Mesenchymal Stem Cells with Recombinant Peptide Pieces, Microencapsulated Islets, and Mesh Bags

“…In fact, it was been reported that MSC-CellSaic increased the release of various cytokines and growth factors, such as IL-8, ENA-78, bFGF, and VEGF [ 10 ]. Other functions of MSCs that contribute to islet viability included inhibition of apoptosis, scaffolding [ 27 ], and protection from cytotoxicity [ 28 , 29 , 30 , 31 , 32 ]. Other than angiogenesis and inhibition of inflammation, the performance of MSCs in the form of CellSaic might also be altered to influence the current study.…”

Research Progress on Mesenchymal Stem Cells for the Treatment of Diabetes and Its Complications

“…Several problems have also emerged with the current treatment with MSCs, including the high number of islet beta cells needed to restore normoglycemia, the low survival rate of cells after transplantation, and the rapid decline in islet function viability after transplantation. In contrast, in a coculture system using MSCs mixed directly with islet β -cells in suspension, the survival rate of islet β cells can reach 50% [ 21 , 22 ]. Direct injection of MSCs into the pancreatic site increases the number of replicating islet cells and islet areas in vivo through physical contact.…”