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Functional comparison of human-induced pluripotent stem cell-derived mesenchymal cells and bone marrow-derived mesenchymal stromal cells from the same donor

Significance Statement

  • iPSC-derived MSC-like progenitor cells (iMPCs) have a high potential for Regenerative Medicine, because unlike primary MSCs they are available in virtually unlimited amounts.
  • iMPCs share mesenchymal characteristics with MSCs: they can give rise to bone, cartilage and fat, express typical MSC surface markers and display a general mesenchymal gene expression program.
  • iMPCs are still a distinct cell population with explicit differences from primary MSCs: they require adapted stimuli for in vitro differentiation and show specific deviations on gene expression level.

 

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

Journal Reference

Diederichs S, Tuan RS.

Stem Cells Dev. 2014 Jul 15;23(14):1594-610.

Department of Orthopedic Surgery, Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.

 

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.

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