Multipotent Adult Progenitor cells (MAPC) are rare progenitor cells present within the bone marrow that have the capacity to differentiate into mesodermal, endodermal and ectodermal lineage cells. The capacity to differentiate into these diverse cell types distinguishes MAPC from Mesenchymal Stem Cells (MSC), and suggests that MAPC may provide biological solutions for tissue repair or regeneration in multiple organ systems (

Jiang Y et al. Nature. 2002; 418:41–9
). We have developed the technology for the large-scale expansion of MAPC with stable phenotype and biological properties. Cell surface marker analysis of MAPC revealed that these cells express low levels of MHC class I, CD44, CD90 and CD49c and are negative for MHC class II, CD45 and CD106 suggesting that MAPC do not express markers associated with the hematopoietic lineage. However, to optimize in vivo utilization, the identification of MAPC immunological properties is necessary. The objectives of the current studies were 1) to determine the immunogenicity of MAPC and 2) to assess the immunomodulatory properties of MAPC. First, MAPC from two different rat strains did not stimulate allogeneic T cells proliferation, while splenocytes of the same rat strains elicited strong proliferative responses in a mixed lymphocytic culture. Second, the immunosuppressive properties of MAPC were investigated using alloactivated T cells. Addition of MAPC at the initiation of a mixed lymphocyte reactions (MLR) suppressed T cell proliferation in a dose dependent manner. The inhibition was detectable at as low as 3,000 MAPC/well. Lymphocyte proliferation in MAPC-containing cultures was inhibited by up to 80% when compared to cultures without MAPC. The ability to inhibit T cell alloresponses was independent of the MHC, allowing the use of “third party” MAPC as inhibitory cells. MAPC also inhibited proliferative responses to the T cell mitogen Concanavalin A (50%), although inhibition required higher MAPC:responder cell ratios. Taken together, these data suggest that MAPC are progenitor cells that do not express markers of the hematopoietic lineage; they are non-immunogenic, suggesting that universal MAPC donors may be used for tissue repair or regeneration; and MAPC exhibit potent immunosuppressive properties, a result which suggests that these calls may be useful in the management and/or prevention of GVHD.

Topics:
immunosuppressive agents, stem cells, t-lymphocytes, cd44 antigens, cd45 antigens, concanavalin a, graft-versus-host disease, growth factor, homing-associated cell adhesion molecule, lymphocyte culture test, mixed

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2005, The American Society of Hematology
2005
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