Faculty Collaboration Database

Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity. Stem Cells 2024 Jul 08;42(7):636-649

Date

04/10/2024

Pubmed ID

38597671

Pubmed Central ID

PMC11228621

DOI

10.1093/stmcls/sxae028

Scopus ID

2-s2.0-85197965337 (requires institutional sign-in at Scopus site)

Abstract

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.

Author List

Chamberlain CS, Prabahar A, Kink JA, Mueller E, Li Y, Yopp S, Capitini CM, Hematti P, Murphy WL, Vanderby R, Jiang P

Author

Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cellular Microenvironment
Exosomes
Humans
Ligaments
Male
MicroRNAs
Rats
Rats, Sprague-Dawley
Wound Healing