Mesenchymal Stem Cells as Feeder Cells for Pancreatic Islet Transplants

Abstract

■ AbstractAllogeneic islet transplant serves as a source for insulinsecreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients.

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

“…Mesenchymal stem cells have shown many unique functions, including release of trophic factors with diverse effects such as improved tissue repair, the reduction of apoptosis, and the promotion of neovascularization . Therefore, they have been used to provide protection for islets from hypoxia‐mediated cell death in islet transplantation .…”

“…Mesenchymal stem cells have shown many unique functions, including release of trophic factors with diverse effects such as improved tissue repair, the reduction of apoptosis, and the promotion of neovascularization. [40][41][42][43] Therefore, they have been used to provide protection for islets from hypoxia-mediated cell death in islet transplantation. 23,[44][45][46] Some studies showed that MSC co-transplantation had a positive effect on islets to tolerate poor oxygenation, but most of these studies focused on accelerating revascularization, rather than directly combating hypoxic damage.…”

Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the Survival of Diabetic Mice after Pancreatic Islet Transplantation

“…The authors demonstrated that encapsulation preserved the islet functionality, and the coencapsulation with mesenchymal stem cells further enhanced islet engraftment . Several groups have been interested in the therapeutic potential of mesenchymal stem cells in order to enhance PEC survival and engraftment: the use of MSCs modulates the host immune response, reduces the need for immunosuppression, decreases inflammatory cytokine production, and promotes the release of trophic and angiogenic molecules . To the best of our knowledge, the use of SVF, instead of mesenchymal stem cells, has not previously been proposed for diabetes treatment, but only for diabetes‐related diseases .…”

Stem Cell Therapy for Islet Regeneration

“…In fact, new results suggest that co-transplantation of stem/precursor cells, particularly MSCs, and islets/IPCs promotes tissue engraftment and beta cell/IPC survival. This theory proposes that stem cells also act as "feeder" cells for the islets, supporting graft protection, tissue revascularisation, and immune acceptance (Sordi et al, 2010).…”