Mesenchymal Stem Cells: The New Immunosuppressants?

ABSTRACT Mesenchymal stem cells are adult stem cells which can differentiate into cells of mesodermal lineage. osteoblasts, chondroblasts and adipocytes. They have an important property of immunosuppression which is mediated mainly through soluble mediators, like interleukin-1, transforming growth factor-β, nitric oxide, indoleamine 2,3 dioxegenase, etc. They have been shown to suppress both naive and antigen experienced T cells, lead to T cell arrest, and suppress Th1 and Th17 responses. They have also been shown to lead to development of tolerogenic dendritic cells, Th2 response and expansion of T regulatory cells. Importantly, MSCs are cells with a low immunogenic potential and hence have been used both in allogenic as well as xenogenic settings. MSCs have shown efficacy in suppressing the development of autoimmune disease in various animal models, like collagen induced arthritis, MRL-lpr mice, EAE mice, etc. They have been used in small human studies, some of which have shown benefit like in systemic lupus erythematosus. Also, they have been used in graft-verus-host disease in humans with promising results. However, a single randomized controlled trial has been done and, thus, their current status remains investigational. It is hoped that they may become part of the armamentarium to control and abberant or excessive immune reponse. Key messages (1) Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate only in one lineage (mesodermal). (2) They were first discovered in the bone marrow and this remains a common source, followed by adipose tissue. There are other sources: Synovial fluid, umbilical cord blood, amniotic fluid, placenta, fetal liver. (3) MSCs are immunosuppressive, the mechanism of which is not fully elucidated, but involves action on other cells mainly through soluble mediators, like TGFβ, IDO, IL-1, NO, etc. (4) MSCs have shown efficacy in various animal models of autoimmune diseases. There have been small human studies, some of which showed benefit, however, a single randomized controlled trial has been done. (5) MSCs may have a role in autoimmune diseases refractory to treatment or as an add onto prevent treatment side effects. How to cite this article Dhir V. Mesenchymal Stem Cells: The New Immunosuppressants? J Postgrad Med Edu Res 2012;46(2):63-68.