Immune Plasticity of Bone Marrow-Derived Mesenchymal Stromal Cells
Isolated from simple bone marrow aspirates, mesenchymal stromal cells (MSCs) can be easily expanded ex vivo and differentiated into various cell lineages. Because they are present in humans of all ages, are harvested in the absence of prior mobilization and preserve their plasticity following gene modification, MSCs are particularly attractive for cell-based medicine. One of the most fascinating properties of ex vivo expanded MSCs is their ability to suppress ongoing immune responses, both in vitro and in vivo. Although not fully understood, the immunosuppressive properties of MSCs have been reported to affect the function of a broad range of immune cells, including T cells, antigen-presenting cells, natural killer cells and B cells. Whereas successful harnessing of these immunosuppressive properties might one day open the door to the development of new cell-based strategies for the control of graft-versus-host and other autoimmune diseases, recent studies suggest that the immune-modulating properties of MSCs are far more complex than first thought. Reminiscent of the dichotomy of function of dendritic cells (DCs), which can act as potent activators or potent suppressors of immune responses, new studies including our own work has shown that MSCs in fact possess the dual ability to suppress or activate immune responses. In this review, we summarize the different biological properties of MSCs and discuss the current literature on the complex mechanism of immune modulation mediated by ex vivo expanded MSCs.
KeywordsMesenchymal stem cells Adult stem cells Antigen presentation Immune suppression Graft-vs-host disease
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- Digirolamo CM, Stokes D, Colter D, Phinney DG, Class R, Prockop DJ (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol 107:275–281PubMedCrossRefGoogle Scholar
- Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T (2002) Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A 99:8932–8937PubMedCrossRefGoogle Scholar
- Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II, Nguyen AT, Malide D, Combs CA, Hall G, Zhang J, Raffeld M, Rogers TB, Stetler-Stevenson W, Frank JA, Reitz M, Finkel T (2006) Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med 203:1235–1247PubMedCrossRefGoogle Scholar
- Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, Santarlasci V, Mazzinghi B, Pizzolo G, Vinante F, Romagnani P, Maggi E, Romagnani S, Annunziato F (2006) Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24:386–398PubMedCrossRefGoogle Scholar
- Le Blanc K, Rasmusson I, Gotherstrom C, Seidel C, Sundberg B, Sundin M, Rosendahl K, Tammik C, Ringden O (2004a) Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol 60:307–315PubMedCrossRefGoogle Scholar
- Reddy P, Liu L, Ren C, Lindgren P, Boman K, Shen Y, Lundin E, Ottander U, Rytinki M, Liu K (2005) Formation of E-cadherin-mediated cell-cell adhesion activates AKT and mitogen activated protein kinase via phosphatidylinositol 3 kinase and ligand-independent activation of epidermal growth factor receptor in ovarian cancer cells. Mol Endocrinol 19:2564–2578PubMedCrossRefGoogle Scholar
- Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A, Peister A, Wang MY, Prockop DJ (2003) Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci U S A 100:2397–2402PubMedCrossRefGoogle Scholar
- Studeny M, Marini FC, Champlin RE, et al (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res. Stem Cells 62:3603–3608Google Scholar