Mesenchymal Stem Cells: Mechanisms of Immunomodulation and …

Cell Transplant. Author manuscript; available in PMC Oct 20, 2010.

Published in final edited form as:

PMCID: PMC2957533

NIHMSID: NIHMS227249

1 Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children and Harvard Medical School, 51 Blossom Street, Boston, Massachusetts 02114, USA

2 Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

3 Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Corresponding author contact information: Martin L. Yarmush, MD, PhD, Shriners Hospitals for Children, 51 Blossom Street, Boston, MA 02114, Telephone: 617-371-4882; Fax: 617-371-4950; Email: ireis/at/sbi.org

*Authors contributed equally

Mesenchymal stem cell (MSC) transplantation has been explored as a new clinical approach to repair injured tissue. A growing corpus of studies have highlighted two important aspects of MSC therapy: (1) MSCs can modulate T-cell mediated immunological responses, and (2) systemically administered MSCs home to sites of ischemia or injury. In this review, we describe the known mechanisms of immunomodulation and homing of MSCs. First, we examine the low immunogenicity of MSCs and their antigen presentation capabilities. Next, we discuss the paracrine interactions between MSCs and innate (dendritic cells (DC)) and adaptive immune cells (T lymphocytes) with a focus on prostaglandin E2 (PGE2), indoleamine 2,3-dioxygenase (IDO) and toll-like receptor (TLR) signaling pathways. We transition to outline the steps of activation, rolling/adhesion, and transmigration of MSCs into target tissues during inflammatory or ischemic conditions. These aspects of MSC grafts - immunomodulation and homing - are contextualized to understand a reported side-effect of MSC therapy, cancer development.

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