Hydrogel Properties May Influence Mesenchymal Stem Cell Lineage Progression Through Modulating GAPDH Activity

Ahmad S. Arabiyat, Silvia Becerra-Bayona, Timothy Kamaldinov, Dany J. Munoz-Pinto, Mariah S. Hahn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Abstract: Cell traction forces, biochemical signals, and cell metabolism are each known to regulate mesenchymal stem cell (MSC) differentiation. Biomaterials have therefore been designed to manipulate cell traction force (via their viscoelasticity and adhesion ligands) to guide MSC fate decisions. Similarly, the type and density of biochemical signals presented by a material have been tailored to influence MSC differentiation. However, the potential impact of biomaterial properties on regulating MSC differentiation through modulating cell metabolism is relatively unstudied. Here, we present data indicating that hydrogel elastic modulus and mesh size regulate MSC differentiation in part through modulating the activity of the metabolic enzyme glyceraldehyde-3-phosphate-dehydrogenase (GAPDH). Toward this end, we first confirm that the differentiation profile of MSCs cultured in 2D on highly elastic, covalently crosslinked poly(ethylene glycol) diacrylate (PEGDA) hydrogels differs substantially from that of MSCs encapsulated within the same hydrogel formulations, indicating a dependence in 3D on a variable(s) beyond elastic modulus. Further results indicate that the GAPDH activity of MSCs in 3D hydrogels is a function of elastic modulus and mesh size, suggesting that GAPDH activity may be one of these variables. Studies in 2D supported a positive correlation between hydrogel elastic modulus and GAPDH activity. Additionally, inhibition of GAPDH activity on 2D surfaces induced alterations in the profiles of key differentiation markers, indicating that GAPDH activity can impact lineage progression. Cumulatively, these findings suggest that the potential impact of hydrogel properties on cell metabolism should be considered when evaluating biomaterial-driven MSC differentiation. Lay Summary: Cell traction forces, biochemical signals, and cell metabolism are each known to regulate mesenchymal stem cell (MSC) differentiation. Biomaterials have therefore been designed to manipulate cell traction force (via their viscoelasticity and adhesion ligands) to guide MSC fate decisions. Similarly, the type and density of biochemical signals presented by a material have been tailored to influence MSC differentiation. However, the impact of biomaterial properties on regulating MSC differentiation through modulating cell metabolism is relatively unstudied. Here, we present data indicating that hydrogel elastic modulus and mesh size regulate MSC differentiation in part through modulating the activity of the metabolic enzyme glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).

Original languageEnglish
Pages (from-to)494-505
Number of pages12
JournalRegenerative Engineering and Translational Medicine
Volume7
Issue number4
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Cell metabolism
  • GAPDH
  • Hydrogel properties
  • MSC differentiation
  • Poly(ethylene glycol) hydrogels

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