The Immunosuppressive Properties of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSC) are a type of multipotent progenitor cell, originally isolated from the bone marrow. In addition to multilineage differentiation and participation in the hematopoietic niche, they exert powerful immunomodulatory effects, which include inhibition of proliferation and function of T cells, B cells, and natural killer cells. These unique properties make MSC of great interest for clinical applications in tissue engineering and immunosuppression. Underlying the MSC-mediated immunomodulatory mechanisms is a nonspecific antiproliferative effect, which is the consequence of cyclin D2 inhibition. Of special interest are the molecular mechanisms, by which MSC influence their target cells. Several studies have been conducted in this field, and the current data suggest roles for indoleamine 2,3-dioxygenase, prostaglandin E2, nitric oxide, histocompatibility locus antigen-G, insulin-like growth factor-binding proteins, and tolerogenic antigen-presenting cells. Understanding these mechanisms is crucial for future use of MSC in research and clinical applications.

Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis

“…1,2 Although hMSC can be obtained from several tissues, they are scarce and their quantity and quality depends on a patient's clinical history, age, gender and genetic background. Most cell therapy protocols use 10-50 million hMSC per treatment, requiring expansion of extracted stem cells ex vivo for about 8 weeks before implantation.…”

Immunogenicity and Immune-Modulating Properties of Human Stem Cells

“…CD4+ and CD8+ T-lymphocytes were equally targeted by hMSC of different origins, and the effects included prevention of lymphocyte activation as well as the suppression of T-cell proliferation regardless of the stimuli used to activate the lymphocytes (Najar et al, 2010). Many different pathways mediating hMSC immunotolerance have been suggested such as suppression of T and B cell proliferation both by cell-mediated and soluble factors (Siegel et al, 2009;Uccelli et al, 2008). Multiple cell-cell interactions and the secretion of soluble factors determine the grade of immunomodulatory capacity by hMSC.…”

“…hMSC were shown to target T-cell proliferation but not their effector function (cytotoxicity). This could be explained by inducing T cells to the G 0 /G 1 cell cycle phase, in part through inhibition of cyclin D expression and up-regulation of p27 kip1 (Giuliani et al, 2011;Ramasamy et al, 2008;Siegel et al, 2009). According to a recent study, T cell inhibition by hMSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies (Giuliani et al, 2011;section 5.2.2.3).…”

“…Thus, here we will explore the most relevant findings in the field of hMSCmediated immunosuppression that have recently gained much attention. hMSC exhibit potent immune-modulating properties which could be useful in numerous clinical applications (section 6.2; Barry et al, 2005;English et al, 2010;Hoogduijn et al, 2010;Le Blanc & Pittenger, 2005;Rasmusson, 2006;Siegel et al, 2009;Sotiropoulou & Papamichail, et al, 2007;Trento & Dazzi, 2010). The immunomodulatory properties of MSC derived from adult human tissues including bone marrow (BM), adipose tissues (AT), umbilical cord blood (CB), and cord Wharton's jelly (WJ) were shown to be comparable (Yoo et al, 2009;Najar et al, 2010).…”

Co-transplantation of third-party umbilical cord blood-derived MSCs promotes engraftment in children undergoing unrelated umbilical cord blood transplantation

“…In addition, MSCs have immunomodulatory properties and have been suggested to support BM stroma. [5][6][7] Therefore, these cells have been explored for use in enhancing engraftment during hematopoietic SCT through human and animal studies. Several clinical studies have reported the facilitation of engraftment by the infusion of MSCs from HSC donors or haploidentical donors to recipients.…”