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Hypoxic Preconditioning Enhances Bone Marrow–Derived Mesenchymal Stem Cell Survival in a Low Oxygen and Nutrient-Limited 3D Microenvironment

Hypoxic Preconditioning Enhances Bone Marrow–Derived Mesenchymal Stem Cell Survival in a Low... ObjectiveSkeletal tissues such as intervertebral disc and articular cartilage possess limited innate potential to regenerate, in part due to their avascularity and low cell density. Despite recent advances in mesenchymal stem cell (MSC)–based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and limited nutrition. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor–β 3 (TGF-β3) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment.DesignMSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-β3, and the global effects on gene expression were examined using microarrays. Subsequently, the effects of preconditioning on MSC survival and extracellular matrix production were examined using low oxygen and nutrient-limited pellet culture experiments.ResultsHypoxic preconditioning resulted in upregulation of genes associated with growth, cell-cell signaling, metabolism, and cell stress response pathways, and significantly enhanced MSC survival for all donors in low oxygen and nutrient-limited pellet culture. In contrast, TGF-β3 preconditioning diminished survival. The nature and magnitude of the effects of preconditioning with either hypoxia or TGF-β3 on glycosaminoglycan production were donor dependent.ConclusionsThese results strongly support the use of hypoxic preconditioning to improve postimplantation MSC survival in avascular tissues such as disc and cartilage. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cartilage SAGE

Hypoxic Preconditioning Enhances Bone Marrow–Derived Mesenchymal Stem Cell Survival in a Low Oxygen and Nutrient-Limited 3D Microenvironment

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References (63)

Publisher
SAGE
Copyright
© The Author(s) 2019
ISSN
1947-6035
eISSN
1947-6043
DOI
10.1177/1947603519841675
Publisher site
See Article on Publisher Site

Abstract

ObjectiveSkeletal tissues such as intervertebral disc and articular cartilage possess limited innate potential to regenerate, in part due to their avascularity and low cell density. Despite recent advances in mesenchymal stem cell (MSC)–based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and limited nutrition. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor–β 3 (TGF-β3) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment.DesignMSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-β3, and the global effects on gene expression were examined using microarrays. Subsequently, the effects of preconditioning on MSC survival and extracellular matrix production were examined using low oxygen and nutrient-limited pellet culture experiments.ResultsHypoxic preconditioning resulted in upregulation of genes associated with growth, cell-cell signaling, metabolism, and cell stress response pathways, and significantly enhanced MSC survival for all donors in low oxygen and nutrient-limited pellet culture. In contrast, TGF-β3 preconditioning diminished survival. The nature and magnitude of the effects of preconditioning with either hypoxia or TGF-β3 on glycosaminoglycan production were donor dependent.ConclusionsThese results strongly support the use of hypoxic preconditioning to improve postimplantation MSC survival in avascular tissues such as disc and cartilage.

Journal

Cartilage – SAGE

Published: Oct 1, 2021

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