The role of exosome-loaded hydrogels in peripheral nerve injury repair

Peripheral nerve injury (PNI) poses significant challenges to patients, often leading to incomplete recovery of sensory and motor function. Current treatments have limitations, prompting researchers to explore innovative approaches. In recent years, exosomes (Exo) derived from stem cells and Schwann cells have emerged as potential therapeutic agents for PNI repair. However, achieving effective and sustained local delivery of Exo remains a hurdle. In this study, researchers from the University of Nebraska Medical Center have developed a groundbreaking solution using Exo-loaded decellularized porcine nerve hydrogels (DNH) to address this challenge.

The study begins by isolating Exo from differentiated human adipose-derived mesenchymal stem cells (hADMSC) with a Schwann cell-like phenotype (dExo). These dExo are then combined with polyethylenimine (PEI) and DNH to create polyplex hydrogels (dExo-loaded pDNH). The cytocompatibility of pDNH with hADMSCs and its ability to support neurite outgrowth of dorsal root ganglions are confirmed.

The sustained release of dExos from dExo-loaded pDNH is observed for at least 21 days both in vitro and in vivo. In a mouse sciatic nerve crush injury model, the dExo-loaded pDNH group demonstrates significant improvements in sensory and motor function recovery and enhanced remyelination compared to control groups. This highlights the synergistic regenerative effects of the hydrogel system.

Interestingly, a negative correlation is observed between the number of colony-stimulating factor-1 receptor (CSF-1R) positive cells and the extent of PNI regeneration at the 21-day post-surgery stage. Subsequent in vitro experiments reveal the potential involvement of the CSF-1/CSF-1R axis in Schwann cells and macrophage interaction, with dExo effectively downregulating CSF-1/CSF-1R signaling.

This study underscores the potential of Exo-loaded hydrogels as a promising therapeutic approach for PNI repair. By harnessing the regenerative properties of Exo and the delivery capabilities of hydrogels, researchers have paved the way for enhanced nerve regeneration and functional recovery. Further exploration of the underlying mechanisms, such as the involvement of the CSF-1/CSF-1R axis, holds promise for advancing our understanding and treatment of PNI.

Liu B, Alimi OA, Wang Y, Kong Y, Kuss M, Krishnan MA, Hu G, Xiao Y, Dong J, DiMaio DJ, Duan B. (2024) Differentiated mesenchymal stem cells-derived exosomes immobilized in decellularized sciatic nerve hydrogels for peripheral nerve repair. J Control Release 368:24-41. [Epub ahead of print]. [article]

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