Induced Pluripotent Stem Cells have Similar Immunogenic and More Potent Immunomodulatory Properties Compared with Bone Marrow-Derived Stromal Cells in Vitro

Abstract

Aim To evaluate the in vitro immunogenic and immunomodulatory properties of induced pluripotent stem cells (iPSCs) compared with bone marrow-derived mesenchymal stromal cells (MSCs). Materials & 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. Conclusion These results provide important information when considering the use of iPSCs in place of MSCs in both regenerative and transplantation medicine.

In vitro and in vivo analysis of human fibroblast reprogramming and multipotency

“…Human dystrophin expression in FOE-treated fibroblast-transplanted mdx mice was detected, indicating that reprogrammed cells were present, and such cells expressed multipotent markers, integrated into the injury site, and expressed dystrophin in mice. Thus, reprogrammed cells showed normal stem cell characteristics, which was consistent with recent studies [18]. Additionally, we confirmed that FOE-treated fibroblasts can differentiate into myofiber-expressed MHC and myogenin in myogenic medium, but few positive myofibers were detected in vitro by immunostaining, suggesting that the regenerative capacity of FOE-treated fibroblasts may be low.…”

Effect of Secreted Molecules of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells on Acute Hepatic Failure Model

“…Consistent with Olivier et al [17] results, we showed that the SW/H method was a highly efficient approach for the induction of adipodifferentiation. Human ESC-MSCs exhibited a higher proliferation rate and longer expansion than BM-MSCs, which agreed with other studies [22]. Of note, the MSC proliferation rates depended on their developmental age, such that adult-derived MSCs proliferated slowly in culture, whereas fetal-derived MSCs proliferated at a faster rate.…”

“…It was demonstrated that ESC-MSCs inhibited CD83 upregulation and IL-12p70 secretion from dendritic cells and enhanced regulatory T cell populations induced by interleukin 2 (IL-2) [22]. Additionally, ESC-MSCs and induced pluripotent stem cell-derived MSCs (iPSC-MSCs) had similar immunogenic properties, but more potent immunomodulatory effects compared with BM-MSCs [22]. Among the molecules secreted from ESC-MSCs, we determined that 35 factors had higher expressions.…”

“…However, the in vitro study demonstrated that ESC-MSCs exhibited more potent antiinflammatory properties than BM-MSCs, which could be attributed to the presence of highly expressed mediators in ESC-MSCs that included angiogenin, IGFBP2, TGF-b1, and MCP1, which have been shown to reduce inflammation [24] or have a pivotal role in positive regulation of the immune system [25]. It was demonstrated that ESC-MSCs inhibited CD83 upregulation and IL-12p70 secretion from dendritic cells and enhanced regulatory T cell populations induced by interleukin 2 (IL-2) [22]. Additionally, ESC-MSCs and induced pluripotent stem cell-derived MSCs (iPSC-MSCs) had similar immunogenic properties, but more potent immunomodulatory effects compared with BM-MSCs [22].…”

Induced Pluripotent Stem Cells Inhibit Bleomycin-Induced Pulmonary Fibrosis in Mice through Suppressing TGF-β1/Smad-Mediated Epithelial to Mesenchymal Transition

“…iPS cells share the similar characteristics such as morphology, self-renewal abilities, gene expression, and surface antigens with ES cells and avoid the ethical and immunorejective problems. More importantly, a recent report has found that iPS cells have more potent immunomodulatory effects compared with bone marrow-derived MSCs in vitro (Schnabel et al, 2014). Accordingly, iPS cells could be suggested as quite promising candidates for cell therapies and regenerative medicine.…”