Functional Comparison of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Cells and Bone Marrow-Derived Mesenchymal Stromal Cells from the Same Donor

Abstract

Mesenchymal stem cells (MSCs) have a high potential for therapeutic efficacy in treating diverse musculoskeletal injuries and cardiovascular diseases, and for ameliorating the severity of graft-versus-host and autoimmune diseases. While most of these clinical applications require substantial cell quantities, the number of MSCs that can be obtained initially from a single donor is limited. Reports on the derivation of MSC-like cells from pluripotent stem cells (PSCs) are, thus, of interest, as the infinite proliferative capacity of PSCs opens the possibility to generate large amounts of uniform batches of MSCs. However, characterization of such MSC-like cells is currently inadequate, especially with regard to the question of whether these cells are equivalent or identical to MSCs. In this study, we have derived MSC-like cells [induced PSC-derived MSC-like progenitor cells (iMPCs)] using four different methodologies from a newly established induced PSC line reprogrammed from human bone marrow stromal cells (BMSCs), and compared the iMPCs directly with the originating parental BMSCs. The iMPCs exhibited typical MSC/fibroblastic morphology and MSC-typical surface marker profile, and they were capable of differentiation in vitro along the osteogenic, chondrogenic, and adipogenic lineages. However, compared with the parental BMSCs, iMPCs displayed a unique expression pattern of mesenchymal and pluripotency genes and were less responsive to traditional BMSC differentiation protocols. We, therefore, conclude that iMPCs generated from PSCs via spontaneous differentiation represent a distinct population of cells which exhibit MSC-like characteristics.

Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium

“…Jin et al, directly induced iPSCs into osteoblastic lineage by culturing iPSCs on poly(caprolactone) scaffolds and adding exogenous osteogenic factors ascorbic acid, beta-glycerophosphate and dexamethasone [21]. Diederichs and Tuan derived MSC-like cells from iPSCs via four different derivation strategies: 1) EB formation, 2) spontaneous differentiation of iPS colonies, 3) mesenchymal co-culture system, and 4) indirect co-culture where iPSCs were seeded on top of cell-free extra cellular matrix from BMSCs and cultured with BMSC-conditioned medium [31]. All four methods succeeded in yielding iPSC-derived MSCs.…”

Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells

“…Nevertheless, directed differentiation of iPSCs into a homogenous population of differentiated cells is technically difficult and can result in immature and/or inferior tissue with regards to cell and extra-cellular matrix organization [23]. Therefore, differentiating iPSCs into an intermediate multipotent cell type, such as MSCs, may not only reduce or eliminate the risk of teratoma formation upon implantation, but also to provide a more homogenous and mature cell type for tissue engineering [24]. Recently, successful differentiation of human and mouse iPSCs into MSC-like cells have been reported This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

Human induced pluripotent stem cells: A new source for brown and white adipocytes

“…The resulting cell cultures are enriched for MSCs through serial cell passaging [30] . Another version of this protocol relies on the spontaneous differentiation of pluripotent stem cells into MSCs [31] . Different research groups have developed additional steps to improve this method.…”

“…Interestingly, MSCs from mesoderm or from neuroectoderm origins can be derived depending on the stromal cells used [34,35] . Finally, MSCs derived from different hiPSC lines generated from different donors, or from the same hiPSC clone using different derivation approaches, have the same adipogenic features [30,31] . MSC adipogenic characteristics are therefore not dependent on the derivation method used.…”