Transplantation of Human Mesenchymal Stem-Cell-Derived Exosomes Immobilized in an Adhesive Hydrogel for Effective Treatment of Spinal Cord Injury

Abstract

Spinal cord injury is among the most fatal diseases. The complicated inhibitory microenvironment requires comprehensive mitigation. Exosomes derived from mesenchymal stem cells (MSCs) are natural biocarriers of cell paracrine secretions that bear the functions of microenvironment regulation. However, the effective retention, release, and integration of exosomes into the injured spinal cord tissue are poorly defined. Herein, an innovative implantation strategy is established using human MSC-derived exosomes immobilized in a peptide-modified adhesive hydrogel (Exo-pGel). Unlike systemic admistration of exosomes, topical transplantation of the Exo-pGel provides an exosome-encapsulated extracellular matrix to the injured nerve tissue, thereby inducing effecient comprehensive mitigation of the SCI microenvironment. The implanted exosomes exhibit efficient retention and sustained release in the host nerve tissues. The Exo-pGel elicits significant nerve recovery and urinary tissue preservation by effectively mitigating inflammation and oxidation. The Exo-pGel therapy presents a promising strategy for effective treatment of central nervous system diseases based on exosome implantation.

Engineered Extracellular Vesicles And Nanoparticles: Promising Tools For Disease Treatment

“…Li et al investigated the roles of Exo-pGel in treatment of spinal cord injury. The Exo-pGel significantly promoted nerve recovery via inhibiting oxidative stress and inflammation 5 . Besides, Chuanjiang He et al give an insight into how EVs engineered as powerful tools in translational medicine 8 .…”

“…This manipulation approach is safe and straightforward, which opens novel insights into targeted-EVs for therapy. Recently, Liming et al used an adhesive hydrogel to enhance the retention of EVs 5 . The EVs were immobilized in an adhesive hydrogel (Exo-pGel) and the encapsulated-EVs can stay at the injured area.…”

“…Cette approche de manipulation est sûre et simple, ce qui ouvre de nouvelles perspectives sur les EV ciblées pour la thérapie. Récemment, Liming et al ont utilisé un hydrogel adhésif pour améliorer la rétention des EVs 5 . Les EV ont été immobilisées dans un hydrogel adhésif (Exo-pGel) et les EV encapsulées peuvent rester dans la zone lésée.…”

“…Li et al ont étudié les rôles d'Exo-pGel dans le traitement des lésions de la moelle épinière. Il a été démontré que l'Exo-pGel favorisait de manière significative la récupération nerveuse en inhibant le stress oxydatif et l'inflammation 5 . En outre, Chuanjiang He et al donnent un aperçu de la façon dont les VE sont conçus comme des outils puissants en médecine translationnelle 8 .…”

BMSC-CM prevents over-differentiation of NSCs to astrocytes by upregulating Smad 6 expression

“…Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for SCI [22]. MSCs, which were rst isolated from bone marrow [23], have the ability to differentiate into three main types of nerve cells.…”