Enhanced tissue production through redox control in stem cell-laden hydrogels

Branden Reid, Junaid M. Afzal, Annemarie M. Mccartney, M. Roselle Abraham, Brian O'Rourke, Jennifer Hartt Elisseeff

Research output: Contribution to journalArticle

Abstract

Cellular bioenergetics and redox (reduction-oxidation) play an important role in cell proliferation and differentiation, key aspects of building new tissues. In the present study, we examined the metabolic characteristics of human adipose-derived stem cells (hASCs) during proliferation and differentiation in both monolayer and three-dimensional biomaterial scaffolds. In monolayer, hASCs exhibited higher glycolysis and lower ox-phos as compared to both adipogenic and osteogenic differentiated cells, and hASCs demonstrated the Warburg effect (aerobic glycolysis). However, reactive oxygen species (ROS) levels increased during adipogenic differentiation, but decreased during osteogenic differentiation. Similarly, a decrease in ROS levels along with a higher mitochondrial membrane potential and viability was observed in hASCs encapsulated in poly(ethylene glycol) (PEG) hydrogels containing an adhesion peptide (RGD), compared to PEG hydrogels with a scrambled control peptide (GRD), demonstrating that adhesion-dependent signaling can also regulate ROS production and bioenergetics. As a result, we hypothesized that we could modulate osteogenesis in PEG hydrogels containing the adhesion peptide (RGD) by further reducing ROS levels using a small therapeutic molecule, L-carnitine, a metabolite with purported antioxidant effects. We observed reduced ROS levels, no effect on mitochondrial membrane potential, and increased osteogenic differentiation and tissue production in cells in the presence of L-carnitine. These results suggest the potential to manipulate tissue production by modulating cellular metabolism.

Original languageEnglish (US)
Pages (from-to)2014-2023
Number of pages10
JournalTissue Engineering - Part A
Volume19
Issue number17-18
DOIs
StatePublished - Sep 1 2013

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Hydrogels
Stem cells
Reactive Oxygen Species
Stem Cells
Polyethylene glycols
Tissue
Oxidation
Oxygen
Peptides
Adhesion
Carnitine
Mitochondrial Membrane Potential
Cell proliferation
Glycolysis
Energy Metabolism
Cell Differentiation
Monolayers
Cell Proliferation
Membranes
Ethylene Glycol

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Enhanced tissue production through redox control in stem cell-laden hydrogels. / Reid, Branden; Afzal, Junaid M.; Mccartney, Annemarie M.; Abraham, M. Roselle; O'Rourke, Brian; Elisseeff, Jennifer Hartt.

In: Tissue Engineering - Part A, Vol. 19, No. 17-18, 01.09.2013, p. 2014-2023.

Research output: Contribution to journalArticle

Reid, Branden ; Afzal, Junaid M. ; Mccartney, Annemarie M. ; Abraham, M. Roselle ; O'Rourke, Brian ; Elisseeff, Jennifer Hartt. / Enhanced tissue production through redox control in stem cell-laden hydrogels. In: Tissue Engineering - Part A. 2013 ; Vol. 19, No. 17-18. pp. 2014-2023.
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