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Mol Pharm. 2019 Oct 7;16(10):4302-4312. doi: 10.1021/acs.molpharmaceut.9b00639. Epub 2019 Aug 26.

Development of MicroRNA-146a-Enriched Stem Cell Secretome for Wound-Healing Applications.

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1
BioIntel Research Laboratory, Department of Chemical and Petroleum Engineering, School of Engineering , University of Kansas , Lawrence , Kansas 66045 , United States.

Abstract

Secretome-based therapies have the potential to become the next generation of viable therapeutic wound repair treatments. However, precise strategies aimed to refine and control the secretome composition are necessary to enhance its therapeutic efficacy and facilitate clinical translation. In this study, we aim to accomplish this by transfecting human adipose-derived stem cells (hASCs) with microRNA-146a, which is a potent regulator of angiogenesis and inflammation. The secretome composition obtained from the transfected hASCs (secretome146a) was characterized and compared to nontransfected hASCs secretome to evaluate changes in angiogenic and anti-inflammatory growth factor, cytokine, and miRNA content. In vitro proliferation, migration, and tubular morphogenesis assays using human umbilical vein endothelial cells (HUVECs) were completed to monitor the proangiogenic efficacy of the secretome146a. Finally, the anti-inflammatory efficacy of the secretome146a was assessed using HUVECs that were activated to an inflammatory state by IL-1β. The resulting HUVEC gene expression and protein activity of key inflammatory mediators were evaluated before and after secretome treatment. Overall, the secretome146a contained a greater array and concentration of therapeutic paracrine molecules, which translated into a superior angiogenic and anti-inflammatory efficacy. Therefore, this represents a promising strategy to produce therapeutic secretome for the promotion of wound repair processes.

KEYWORDS:

angiogenesis; anti-inflammatory agents; extracellular vesicles; microRNA; secretome

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