| Summary: | <p>Mesenchymal stem cells (MSCs) are adult stem cells derived from soft tissue or bone marrow (BM) and are widely investigated due to their multi-potential differentiation and immunomodulatory abilities. They are skeletal lineage progenitors, being able to differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, myocytes and more. However, MSCs are limited for use in clinical settings and for in vitro purposes. The main limitation for in vitro-based research is cell senescence, which occurs during sub-culturing of MSCs. MSC-like cells, termed induced MSCs (iMSCs), are derived from induced pluripotent stem cells (iPSCs) and display similar characteristics as MSCs. Yet, these iMSCs are not restricted by senescence, making them an attractive alternative source. The differentiation of iPSCs into iMSCs has been recently described, however mechanisms that underlie this process and the comparison between iMSCs and BM-MSCs are largely lacking. </p> <p>This study aimed to identify a suitable protocol for the differentiation of iPSCs into iMSCs. The chosen protocol consists of a 14-day phase 1 followed by a passaging protocol, thus selecting for cells primed for stable differentiation into the mesenchymal lineage. Detailed characterisation of the mechanistic actions during the differentiation was documented. Moreover, iMSCs were compared to BM-MSCs on a proteomic and transcriptomic level. Known mesenchymal stem cell (MSC) and pluripotency markers expression levels were measured using mass cytometry (CyTOF) and RNA sequencing techniques. Results display a gradual loss of pluripotency gene and protein expression as well as an upregulation of MSC markers, indeed indicating a shift towards a more mesenchymal-like stem cell type. However distinct features between bone-marrow derived MSCs and iMSCs are observed, including an apparent lack of adipogenic differentiation in iMSCs despite osteogenic differentiation potential. </p>
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