Comparisons of phenotype and immunomodulatory capacity among rhesus bone-marrow-derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts.
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.


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.
Department of Surgery, University of Minnesota, St. Paul, MN, USA.|Schulze Diabetes Institute, University of Minnesota, St. Paul, MN, USA.
Gregory M
GM
Sindberg
Veterinary Population Medicine Department, University of Minnesota, St. Paul, MN, USA.|Stem Cell Institute, University of Minnesota, St. Paul, MN, USA.
Beth A
BA
Lindborg
Biostatistical Design and Analysis Center, Clinical and Translational Science Institute, University of Minnesota, St. Paul, MN, USA.
Qi
Q
Wang
Stem Cell Institute, University of Minnesota, St. Paul, MN, USA.|Veterinary and Biomedical Sciences Department, University of Minnesota, St. Paul, MN, USA.
Christina
C
Clarkson
Department of Surgery, University of Minnesota, St. Paul, MN, USA.|Schulze Diabetes Institute, University of Minnesota, St. Paul, MN, USA.
Melanie
M
Graham
Hematology Branch, National Heart Lung Blood Institute, Rockville, MD, USA.
Robert
R
Donahue
Department of Surgery, University of Minnesota, St. Paul, MN, USA.|Schulze Diabetes Institute, University of Minnesota, St. Paul, MN, USA.
Bernhard J
BJ
Hering
Stem Cell Institute, University of Leuven, Leuven, Belgium.
Catherine M
CM
Verfaillie
Department of Surgery, University of Minnesota, St. Paul, MN, USA.|Schulze Diabetes Institute, University of Minnesota, St. Paul, MN, USA.
Pratima
P
Bansal-Pakala
Veterinary Population Medicine Department, University of Minnesota, St. Paul, MN, USA.|Stem Cell Institute, University of Minnesota, St. Paul, MN, USA.
Timothy D
TD
O'Brien
D053687:Adult Stem Cells / Q000276:immunology*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D007165:Immunosuppression Therapy; D008253:Macaca mulatta; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D010641:Phenotype; D012867:Skin / Q000166:cytology
T-cell suppression; cellular therapy; immunophenotype