Induced pluripotent stem cells have similar immunogenic and more potent immunomodulatory properties compared with bone marrow-derived stromal cells in vitro.
OBJECTIVE
To evaluate the in vitro immunogenic and immunomodulatory properties of induced pluripotent stem cells (iPSCs) compared with bone marrow-derived mesenchymal stromal cells (MSCs).


METHODS
Mouse embryonic fibroblasts (MEFs) were isolated from C3HeB/FeJ and C57BL/6J mice, and reprogrammed to generate iPSCs. Mixed leukocyte reactions were performed using MHC-matched and -mismatched responder leukocytes and stimulator leukocytes, iPSCs or MSCs. To assess immunogenic potential, iPSCs and MSCs were used as stimulator cells for responder leukocytes. To assess immunomodulatory properties, iPSCs and MSCs were cultured in the presence of stimulator and responder leukocytes. MEFs were used as a control.


RESULTS
iPSCs had similar immunogenic properties but more potent immunomodulatory effects than MSCs. Co-culture of MHC-mismatched leukocytes with MHC-matched iPSCs resulted in significantly less responder T-cell proliferation than observed for MHC-mismatched leukocytes alone and at more responder leukocyte concentrations than with MSCs. In addition, MHC-mismatched iPSCs significantly reduced responder T-cell proliferation when co-cultured with MHC-mismatched leukocytes, while MHC-mismatched MSCs did not.


CONCLUSIONS
These results provide important information when considering the use of iPSCs in place of MSCs in both regenerative and transplantation medicine.
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA.
Lauren V
LV
Schnabel
Christian M
CM
Abratte
John C
JC
Schimenti
M Julia Bevilaqua
MJ
Felippe
Jennifer M
JM
Cassano
Teresa L
TL
Southard
Jessica A
JA
Cross
Lisa A
LA
Fortier
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D056747:Immunomodulation; D057026:Induced Pluripotent Stem Cells / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
D016207:Cytokines
allogeneic stem cell therapy; immunogenicity; immunomodulatory; induced pluripotent stem cell; mesenchymal stromal cell; transplantation medicine