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.

Keywords: exosomes; immunomodulation; mesenchymal stem cells; nanotubes; pancreatic islets; transplantation.

Figure 1

MSC immunomodulatory effects. MSC can exert an immunomodulatory effect on target cells through several mechanisms including biologically active factors (cytokine, chemokines, growth factors) and exosomes which contain lipids, proteins, miRNA. Red arrows indicate down-regulation, green arrows indicate up-regulation.

Figure 2

Role of MSC in islet transplantation. MSCs, either autologous or allogenic, have the potential to enhance the efficiency and success rate of treatments involving transplanted pancreatic islets through several mechanisms including regeneration of β-cell mass, generation of vascularized islet-like organoids and modifying the microenvironment via paracrine effects of their secretome and EXOs. In addition, MSC-loaded magnetic carbon nanotubes can play an important role in biomedical application enhancing the homing of stem cells towards the target organ. MSC: mesenchymal stem cells, MPC: mesangiogenic progenitor cells, iPSC: induced pluripotent stem cells, EXO: exosome-derived MSCs.