The role of extracellular matrix expression, ERK1/2 signaling and cell cohesiveness for cartilage yield from iPSCs

• Verfasst von: Buchert, Justyna [VerfasserIn]
• Verfasst von: Diederichs, Solvig [VerfasserIn]
• Verfasst von: Kreuser, Ursula [VerfasserIn]
• Verfasst von: Merle, Christian [VerfasserIn]
• Verfasst von: Richter, Wiltrud [VerfasserIn]
• Titel: The role of extracellular matrix expression, ERK1/2 signaling and cell cohesiveness for cartilage yield from iPSCs
• Verf.angabe: Justyna Buchert, Solvig Diederichs, Ursula Kreuser, Christian Merle and Wiltrud Richter
• E-Jahr: 2019
• Jahr: 2 September 2019
• Umfang: 20 S.
• Fussnoten: Gesehen am 02.12.2019
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2019
• Band/Heft Quelle: 20(2019,17) Artikel-Nummer 4295, 20 Seiten
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms20174295
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cartilage regeneration
• Sach-SW: ERK1/2 signaling
• Sach-SW: extracellular matrix
• Sach-SW: induced pluripotent stem cells
• Sach-SW: mesenchymal stromal cells
• K10plus-PPN: 168396697X
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Current therapies involving chondrocytes or mesenchymal stromal cells (MSCs) remain inefficient in restoring cartilage properties upon injury. The induced pluripotent stem-cell (iPSC)-derived mesenchymal progenitor cells (iMPCs) have been put forward as a promising alternative cell source due to their high proliferation and differentiation potential. However, the observed cell loss during in vitro chondrogenesis is currently a bottleneck in establishing articular chondrocyte generation from iPSCs. In a search for candidate mechanisms underlying the low iPSC-derived cartilage tissue yield, global transcriptomes were compared between iMPCs and MSCs and the cell properties were analyzed via a condensation assay. The iMPCs had a more juvenile mesenchymal gene signature than MSCs with less myofibroblast-like characteristics, including significantly lower ECM- and integrin-ligand-related as well as lower α-smooth-muscle-actin expression. This correlated with less substrate and more cell-cell adhesion, impaired aggregate formation and consequently inferior cohesive tissue properties of the iMPC-pellets. Along lower expression of pro-survival ECM molecules, like decorin, collagen VI, lumican and laminin, the iMPC populations had significantly less active ERK1/2 compared to MSCs. Overall, this study proposes that this ECM and integrin-ligand shortage, together with insufficient pro-survival ERK1/2-activity, explains the loss of a non-aggregating iMPC sub-fraction during pellet formation and reduced survival of cells in early pellets. Enhancing ECM production and related signaling in iMPCs may be a promising new means to enrich the instructive microenvironment with pro-survival cues allowing to improve the final cartilage tissue yield from iPSCs.