| Abstract: | Current sources of human stem cells include embryonic stem cells (ESCs) and adult stem cells (ASCs). However, concerns exist with either source: ESCs, with its significant ethical considerations, tumorigenicity concerns, and paucity of cell lines; and ASCs, which are possibly more limited in proliferative and differentiation potential. Thus, the search continues for an ethically conducive, easily accessible, and high-yielding source of stem cells. Our research group has isolated multipotent cells from the human term placenta, a temporary organ which is discarded after birth. Placenta-derived multipotent cells (PDMCs) exhibit similar markers as bone marrow mesenchymal stem cells, including CD105 and CD73, as well as ESC markers such as SSEA-4; and can differentiate into cell phenotypes representative of all three germ layers. Moreover, PDMCs have significant immunomodulatory effects towards allogeneic lymphocytes of both the innate and adaptive arm. PDMCs suppress allogeneic T lymphocyte proliferation, and express indoleamine 2,3-dioxygenase as well as intracellular HLA-G. Mechanistically, suppression of lymphocyte reactivity by PDMCs is not due to cell death, but decreased cell proliferation and increased numbers of regulatory T cells. Several effector functions of natural killer lymphocytes (NKs) are also suppressed by PDMCs, including interferon-γ (IFN-γ) secretion and cytotoxicity. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhances such immunosuppressive effects. With its broad immunosuppressive properties and multilineage differentiation capacity, PDMCs may represent a potential cell source for therapeutic use. |
