iPSC-derived MSCs are Functionally and Genetically Different from BM-MSCs.

There has been considerable interest in the generation of functional mesenchymal stromal cell (MSC) preparations from induced pluripotent stem cells (iMSCs) and this is now regarded as a potential source of unlimited, standardized, high-quality cells for therapeutic applications in regenerative medicine. While iMSCs meet minimal criteria for defining MSCs in terms of marker expression there are substantial differences in terms of trilineage potential, specifically a marked reduction in chondrogenic and adipogenic propensity in iMSCs compared to bone marrow-derived (BM) MSCs. To reveal the cellular basis underlying these differences we conducted phenotypic, functional and genetic comparisons between iMSCs and BM-MSCs. We found that iMSCs express very high levels of both KDR and MSX2 compared to BM-MSCs. In addition, BM-MSCs had significantly higher levels of PDGFRα. These distinct gene expression profiles were maintained during culture expansion suggesting that prepared iMSCs are more closely related to vascular progenitor cells (VPCs). Although VPCs can differentiate along the chondrogenic, osteogenic and adipogenic pathways, they require different inductive conditions compared to BM-MSCs. These observations suggest to us that iMSCs, based on current widely used preparation protocols, do not represent a true alternative to primary MSCs isolated from bone marrow. Further, this study highlights the fact that high levels of expression of typical MSC markers such as CD73, CD90 and CD105 are insufficient to distinguish MSCs from other mesodermal progenitors in differentiated iPSC cultures. SIGNIFICANCE STATEMENT: The generation of mesenchymal stromal cells from induced pluripotent stem cells (iMSCs) has been proposed as an alternative strategy for obtaining unlimited sources of these cells of defined quality and capable of meeting increasing demands for research and therapeutic applications. However, there are distinctions between primary MSCs and iMSCs in terms of phenotype and differentiation. We show that iMSCs share phenotypic traits with BM-MSCs in terms of standard marker expression but show marked differences in gene expression, especially in genes associated with vascular progenitor cells. These differences may explain the altered differentiation propensity of human iMSCs compared to primary MSCs. © AlphaMed Press 2019.