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Mechanical environment modulates biological properties of oligodendrocyte progenitor cells.

ABSTRACT: Myelination and its regenerative counterpart remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo CNS environment. Little is known of how variation in mechanical properties over the physiological range affects OPC biology. Here, we show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and differentiation capacity in vitro depend on the mechanical stiffness of polymer hydrogel substrata. Most of these properties are optimal at the intermediate values of CNS tissue stiffness. Moreover, many of these properties measured for cells on gels of optimal stiffness differed significantly from those measured on glass or polystyrene. The dependence of OPC differentiation on the mechanical properties of the extracellular environment provides motivation to revisit results obtained on nonphysiological, rigid surfaces. We also find that OPCs stiffen upon differentiation, but that they do not change their compliance in response to substratum stiffness, which is similar to embryonic stem cells, but different from adult stem cells. These results form the basis for further investigations into the mechanobiology of cell function in the CNS and may specifically shed new light on the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis.

SUBMITTER: Jagielska A

PROVIDER: S-EPMC5915215 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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Mechanical environment modulates biological properties of oligodendrocyte progenitor cells.

Jagielska Anna A Norman Adele L AL Whyte Graeme G Vliet Krystyn J Van KJ Guck Jochen J Franklin Robin J M RJ

Stem cells and development 20120703 16

Myelination and its regenerative counterpart remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo C ...[more]

PMID: 22646081

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Project description:The progression of mesenchymal stem cell-based therapy from concept to cure closely depends on the optimization of conditions that allow a better survival and favor the cells to achieve efficient liver regeneration. We have previously demonstrated that adult-derived human liver stem/progenitor cells (ADHLSC) display significant features that support their clinical development. The current work aims at studying the impact of a sustained pro-inflammatory environment on the principal biological features of ADHLSC in vitro. ADHLSC from passages 4-7 were exposed to a cocktail of inflammatory cytokines for 24 h and 9 days and subsequently analyzed for their viability, expression, and secretion profiles by using flow cytometry, RT-qPCR, and antibody array assay. The impact of inflammation on the hepatocytic differentiation potential of ADHLSC was also evaluated. ADHLSC treated with a pro-inflammatory cocktail displayed significant decrease of cell yield at both times of treatment while cell mortality was observed at 9 days post-priming. After 24 h, no significant changes in the immuno-phenotype of ADHLSC expression profile could be noticed while after 9 days, the expression profile of relevant markers has changed both in the basal conditions and after inflammation treatment. Inflammation cocktail enhanced the release of IL-6, IL-8, CCL5, monocyte-chemo-attractant protein-2 and 3, CXCL1/GRO, and CXCL5/ENA78. Furthermore, while IP-10 secretion was increased after 24 h priming, granulocyte macrophage colony-stimulating factor enhanced secretion was noticed after 9 days treatment. Finally, priming of ADHLSC did not affect their potential to differentiate into hepatocyte-like cells. These results indicate that ADHLSCs are highly sensitive to inflammation and respond to such signals by adjusting their gene and protein expression. Accordingly, monitoring the inflammatory status of patients at the time of cell transplantation, will certainly help in enhancing ADHLSC safety and efficiency.

Dataset Information

Mechanical environment modulates biological properties of oligodendrocyte progenitor cells.

Publications

Mechanical environment modulates biological properties of oligodendrocyte progenitor cells.

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