Modulating Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity

ABSTRACT: Mesenchymal stromal cells (MSCs) hold great promise in regenerative medicine due to their potential to promote tissue repair and regeneration. However, applying MSC-based cell therapy in actual clinical settings remains challenging due to issues such as immunocompatibility and cell stability. Recent shifts in therapeutic strategies have highlighted MSC-derived exosomes, small vesicles carrying various bioactive molecules, as a promising cell-free therapy to promote tissue regeneration. However, it remains largely unknown regarding the ability to customize the content of MSC-derived exosomes, how alterations in the MSC microenvironment influence exosome content, and the effects of such alterations on healing efficiency and mechanical properties in tissue repair when utilized as a therapy. In this study, we used an in vitro system of human MSC-derived exosomes and an in vivo rat ligament injury model to address these questions. We found a context-dependent correlation between exosomal and parent cell RNA content. Under native conditions, the correlation was moderate but heightened with microenvironmental changes. In vivo rat ligament injury model showed that MSC-derived exosomes increased ligament max load and stiffness. We also found that changes in the MSCs' microenvironment significantly influence the mechanical properties driven by exosome treatment. 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.

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE245884 | GEO | 2024/07/17

REPOSITORIES: GEO