Mesenchymal Stromal Cells in Transplantation Rejection and Tolerance

Abstract

Mesenchymal stromal cells (MSCs) have recently emerged as promising candidates for cellbased immunotherapy in solid organ transplantation (SOT). In addition to immune modulation, MSCs possess proreparative properties and preclinical studies indicate that MSCs have the capacity to prolong graft survival and in some cases induce tolerance. Currently, the application of MSCs in SOT is being evaluated in phase I/II clinical trials. Whereas the mechanisms of action used by MSC immunomodulation have been somewhat elucidated in vitro, the data from preclinical transplant models have been unclear. Furthermore, the optimal timing, dose, and route of administration remain to be elucidated. Importantly, MSCs have the ability to sense their environment, which may influence their function. In this article, we discuss the impact of the local microenvironment on MSCs and the mechanisms of MSC immunomodulation in the setting of SOT.

Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I–II, open-label, clinical study

“…Specifically, MSCs have been shown to decrease effector T cell response while promoting the emergence of regulatory T cells (Treg) [6]. These MSC properties suggest that they could be particularly attractive in solid organ transplantation (SOT) [7,8], and a consortium of European academic centres studying this subject has been created (http:// www.misot.eu). The first randomized controlled trial, evaluating the effects of autologous MSCs in living-related kidney transplantation has been performed in China [9].…”

iPSC-MSCs Combined with Low-Dose Rapamycin Induced Islet Allograft Tolerance Through Suppressing Th1 and Enhancing Regulatory T-Cell Differentiation

“…However, it does not have an ideal postoperative survival time because of immune rejection and islet toxicity of immunosuppressive agents [1,2]. The immunosuppressive effect and low immunogenicity of mesenchymal stem cells (MSCs) make them ideal candidates for immunosuppressive strategies [3,4]. Adult MSCs have been used widely in the allogeneic heart [5][6][7][8][9][10][11], liver [12], islet [13][14][15][16][17], kidney [18,19], and composite tissue transplants [20,21].…”

Conversion of Th17 into IL-17Aneg Regulatory T Cells: A Novel Mechanism in Prolonged Allograft Survival Promoted by Mesenchymal Stem Cell–Supported Minimized Immunosuppressive Therapy

“…In association with moderate doses of certain immunosuppressive drugs, mesenchymal stem cells (MSCs) have shown unique immunoregulatory properties and promote long-term graft acceptance (17)(18)(19)(20). Various studies, including our own, have shown that MSC-mediated tolerance in vivo can be maintained by T reg cells (21)(22)(23)(24)(25)(26).…”