Scalable generation of mesenchymal stem cells and adipocytes from human pluripotent stem cells

Manale Karam, Ihab Younis, Noor R. Elareer, Sara Nasser, Essam M. Abdelalim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Human pluripotent stem cells (hPSCs) can provide unlimited supply for mesenchymal stem cells (MSCs) and adipocytes that can be used for therapeutic applications. Here we developed a simple and highly efficient all-trans-retinoic acid (RA)-based method for generating an off-the-shelf and scalable number of human pluripotent stem cell (hPSC)-derived MSCs with enhanced adipogenic potential. We showed that short exposure of multiple hPSC lines (hESCs/hiPSCs) to 10 µM RA dramatically enhances embryoid body (EB) formation through regulation of genes activating signaling pathways associated with cell proliferation, survival and adhesion, among others. Disruption of cell adhesion induced the subsequent differentiation of the highly expanded RA-derived EB-forming cells into a pure population of multipotent MSCs (up to 1542-fold increase in comparison to RA-untreated counterparts). Interestingly, the RA-derived MSCs displayed enhanced differentiation potential into adipocytes. Thus, these findings present a novel RA-based approach for providing an unlimited source of MSCs and adipocytes that can be used for regenerative medicine, drug screening and disease modeling applications.

Original languageEnglish
Article number710
JournalCells
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Adipogenic differentiation
  • Apoptosis
  • HPSCs
  • MSCs
  • Proliferation
  • RNA-Seq
  • Retinoic acid

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