Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity.

Autor:	Chamberlain CS; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, United States., Prabahar A; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, United States.; Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, United States., Kink JA; Department of Medicine, University of Wisconsin, Madison, WI 53706, United States.; Carbone Cancer Center, University of Wisconsin, Madison, WI 53706, United States., Mueller E; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, United States., Li Y; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, United States., Yopp S; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, United States., Capitini CM; Carbone Cancer Center, University of Wisconsin, Madison, WI 53706, United States.; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, United States., Hematti P; Department of Medicine, University of Wisconsin, Madison, WI 53706, United States.; Carbone Cancer Center, University of Wisconsin, Madison, WI 53706, United States.; Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, United States., Murphy WL; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53706, United States.; Carbone Cancer Center, University of Wisconsin, Madison, WI 53706, United States.; Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, United States., Vanderby R; Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, United States., Jiang P; Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, United States.; Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, United States.; Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States.
Jazyk:	angličtina
Zdroj:	Stem cells (Dayton, Ohio) [Stem Cells] 2024 Jul 08; Vol. 42 (7), pp. 636-649.
DOI:	10.1093/stmcls/sxae028
Abstrakt:	Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored. In this study, we used an in vitro system to compare the priming of human MSCs by 2 inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency. Different microenvironmental stimuli used to prime MSCs in vitro affected their exosomal microRNAs and mRNAs, influencing ligament healing. Exosomes derived from untreated MSCs significantly enhance the mechanical properties of healing ligaments, in contrast to those obtained from MSCs primed with inflammation-inducers, which not only fail to provide any improvement but also potentially deteriorate the mechanical properties. Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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