Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Are Functionally and Genetically Different From Bone Marrow-Derived Mesenchymal Stromal Cells. (6th March 2019)

• Record Type: Journal Article
• Authors: Xu, Maojia; Shaw, Georgina; Murphy, Mary; Barry, Frank
• Is Part Of: Stem cells. Volume 37:Number 6(2019)
• Page Start: 754
• Page End: 765
• Publication Date: 2019-03-06
• Subjects: Mesenchymal stromal cells -- Induced pluripotent stem cells -- iPSC-derived mesenchymal stromal cells -- Vascular progenitor cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2993
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : There has been considerable interest in the generation of functional mesenchymal stromal cell (MSC) preparations from induced pluripotent stem cells (iPSCs) and this is now regarded as a potential source of unlimited, standardized, high-quality cells for therapeutic applications in regenerative medicine. Although 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 with 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 with 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 with 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 BM. Furthermore, 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 induced pluripotent stem cell cultures. Stem Cells 2019;37:754–765 : Abstract : Distinct gene expression profiles between bone marrow derived-mesenchymal stromal cells and induced mesenchymal stromal cells suggested that the latter one were more similar to vascular progenitor cells. The known cellular plasticity of vascular progenitor cells underpinned the potential of induced mesenchymal stromal cells in trilineage differentiation and interpreted the significant divergence in multipotency between both cell groups. Traditional characterization methods cannot distinguish mesenchymal stromal cells from vascular progenitor cells, which, therefore, increase a risk of lineage misidentification.