Mesenchymal Stem Cell in Pancreatic Islet Transplantation

Abstract

Pancreatic islet transplantation is a therapeutic option for achieving physiologic regulation of plasma glucose in Type 1 diabetic patients. At the same time, mesenchymal stem cells (MSCs) have demonstrated their potential in controlling graft rejection, the most fearsome complication in organ/tissue transplantation. MSCs can interact with innate and adaptive immune system cells either through direct cell-cell contact or through their secretome including exosomes. In this review, we discuss current findings regarding the graft microenvironment of pancreatic islet recipient patients and the crucial role of MSCs operation as cell managers able to control the immune system to prevent rejection and promote endogenous repair. We also discuss how challenging stressors, such as oxidative stress and impaired vasculogenesis, may jeopardize graft outcomes. In order to face these adverse conditions, we consider either hypoxia-exposure preconditioning of MSCs or human stem cells with angiogenic potential in organoids to overcome islets’ lack of vasculature. Along with the shepherding of carbon nanotubes-loaded MSCs to the transplantation site by a magnetic field, these studies look forward to exploiting MSCs stemness and their immunomodulatory properties in pancreatic islet transplantation.

Advancements in innate immune regulation strategies in islet transplantation

“…By far, the most prevalent source of MSCs in clinical trials is adult bone marrow, followed by adipose tissue and puerperal discards such as umbilical cord tissue and placental cells ( 80 ). In islet transplantation, MSCs can promote the polarization of mononuclear cells/macrophages to the M2 phenotype by secreting exosomes and cytokines including Indoleamine 2,3-dioxygenase (IDO), IL-4 and IL-10 ( 81 ), while inhibiting their differentiation to the M1 phenotype, reducing the production of IL-12 and blocking the maturation of dendritic cells; the ability of immature dendritic cells to present antigen will be diminished and ultimately weaken T-cell function, thus improving the survival rate of the transplanted islet ( 82 ). At present, the MSC research directions are mainly the selection of subgroups under different types and states and MSC engineering.…”

Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation

“…Pancreatic islet transplantation is a therapeutic option for treating Type I diabetes; however, acute islet loss is a significant complication of this procedure. Barachini et al reviewed various approaches using MSCs and MSC-EVs to create a more conducive immune microenvironment, aiming to reduce graft rejection and promote early vascularization to support graft survival [ 70 ]. Mrahleh et al reported that MSCs primed with IFN-γ and TNF-α exhibited an immunomodulatory effect on CD4 + and CD8 + T cells by producing tolerogenic dendritic cells, which inhibit antigen-specific T cell responses via induction T cell anergy [ 68 ].…”

Subcutaneous device-free islet transplantation

“…However, some studies have suggested that the secretion of some trophic factors may play a role in this process. Although MSCs can be derived from different tissues in the body, most studies have indicated that the secretion of trophic factors, which promote islet revascularization, is responsible for improving metabolic graft function ( 8 ).…”

“…However, the shortage of pancreatic donors poses a significant obstacle for type 1 diabetes patients, as well as hindering the clinical application of islet transplantation. Recently cell-replacement therapies using functional insulin-producing pancreatic β cells generated from stem cell differentiation or transdifferentiation offer potential treatment options ( 8 ). However, these approaches still have several limitations compared to somatic islets derived from the same individual.…”