Gregory M Sindberg1,2, Beth A Lindborg3,4, Qi Wang5, Christina Clarkson4,6, Melanie Graham1,2, Robert Donahue7, Bernhard J Hering1,2, Catherine M Verfaillie8, Pratima Bansal-Pakala1,2, Timothy D O'Brien3,4. 1. Department of Surgery, University of Minnesota, St. Paul, MN, USA. 2. Schulze Diabetes Institute, University of Minnesota, St. Paul, MN, USA. 3. Veterinary Population Medicine Department, University of Minnesota, St. Paul, MN, USA. 4. Stem Cell Institute, University of Minnesota, St. Paul, MN, USA. 5. Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, St. Paul, MN, USA. 6. Veterinary and Biomedical Sciences Department, University of Minnesota, St. Paul, MN, USA. 7. Hematology Branch, National Heart Lung Blood Institute, Rockville, MD, USA. 8. Stem Cell Institute, University of Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4(+) and CD8(+) lymphocyte populations have not been reported. METHODS: We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. RESULTS AND CONCLUSIONS: Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable.
BACKGROUND: Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side-by-side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4(+) and CD8(+) lymphocyte populations have not been reported. METHODS: We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT-PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type. RESULTS AND CONCLUSIONS: Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable.
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