Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

作者: Chelsey Dunham , Necat Havlioglu , Aaron Chamberlain , Spencer Lake , Gretchen Meyer

DOI: 10.1096/FJ.202001274R

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摘要: Fibrosis is driven by a misdirected cell response causing the overproduction of extracellular matrix and tissue dysfunction. Numerous pharmacological strategies have attempted to prevent fibrosis but attained limited efficacy with some detrimental side effects. While stem treatments provided more encouraging results, they exhibited high variability not always improved function. To enhance efficacy, we evaluated whether mechanical memory could direct response. We hypothesized that mechanically pre-conditioning on soft (soft priming) will delay adipose-derived (ASC) transition pro-fibrotic phenotype, expanding their regenerative potential, improving healing in complex environment. Primary ASCs isolated from rat human subcutaneous fat memory, demonstrated delayed stiffness following two weeks priming including decreased area, actin coherency, production compared cells stiff substrates. Soft primed injected into our model post-traumatic elbow contracture histological evidence anterior capsule increased range-of-motion when joint mechanics. These findings suggest exploiting strategically controlling culture environment during expansion may improve cell-based therapies targeting fibrosis.

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