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Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes.

ABSTRACT: Traumatic spinal cord injury is a fatal acute event without effective clinical therapies. Following the trauma, immediate neural protection and microenvironment mitigation are vitally important for nerve tissue repair, where stem cell-based therapies could be eclipsed by the deficiency of cells due to the hostile microenvironment as well as the transport and preservation processes. Effective emergency strategies are required to be convenient, biocompatible, and stable. Herein, we assess an emergency cell-free treatment using mesenchymal stem cell-derived exosomes, which have proven capable of comprehensive mitigation of the inhibitory lesion microenvironment. The clinically validated fibrin glue is utilized to encapsulate the exosomes and in-situ gelates in transected rat spinal cords to provide a substrate for exosome delivery as well as nerve tissue growth. The emergency treatment alleviates the inflammatory and oxidative microenvironment, inducing effective nerve tissue repair and functional recovery. The therapy presents a promising strategy for effective emergency treatment of central nervous system trauma.

SUBMITTER: Mu J

PROVIDER: S-EPMC8739259 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes.

Mu Jiafu J Wu Jiahe J Cao Jian J Ma Teng T Li Liming L Feng Shiqing S Gao Jianqing J

Asian journal of pharmaceutical sciences 20211029 6

Traumatic spinal cord injury is a fatal acute event without effective clinical therapies. Following the trauma, immediate neural protection and microenvironment mitigation are vitally important for nerve tissue repair, where stem cell-based therapies could be eclipsed by the deficiency of cells due to the hostile microenvironment as well as the transport and preservation processes. Effective emergency strategies are required to be convenient, biocompatible, and stable. Herein, we assess an emerg ...[more]

PMID: 35027955

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Project description:Spinal cord injury (SCI) can cause severe irreversible motor dysfunction and even death. Neural stem cell (NSC) transplantation can promote functional recovery after acute SCI in experimental animals, but numerous issues, including low-transplanted cell survival rate, cell de-differentiation, and tumor formation need to be resolved before routine clinical application is feasible. Recent studies have shown that transplanted stem cells facilitate regeneration through release of paracrine factors. Small extracellular vesicles (sEVs), the smallest known membrane-bound nanovesicles, are involved in complex intercellular communication systems and are an important vehicle for paracrine delivery of therapeutic agents. However, the application of NSC-derived small extracellular vesicles (NSC-sEVs) to SCI treatment has not been reported. We demonstrate that NSC-sEVs can significantly reduce the extent of SCI, improve functional recovery, and reduce neuronal apoptosis, microglia activation, and neuroinflammation in rats. Furthermore, our study suggests that NSC-sEVs can regulate apoptosis and inflammatory processes by inducing autophagy. In brief, NSC-sEVs increased the expression of the autophagy marker proteins LC3B and beclin-1, and promoted autophagosome formation. Following NSC-sEV infusion, the SCI area was significantly reduced, and the expression levels of the proapoptotic protein Bax, the apoptosis effector cleaved caspase-3, and the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were significantly reduced, whereas the expression level of the anti-apoptotic protein Bcl-2 was upregulated. In the presence of the autophagy inhibitor 3MA, however, these inhibitory effects of NSC-sEVs on apoptosis and neuroinflammation were significantly reversed. Our results show for the first time that NSC-sEV treatment has the potential to reduce neuronal apoptosis, inhibit neuroinflammation, and promote functional recovery in SCI model rats at an early stage by promoting autophagy.

Dataset Information

Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes.

Publications

Rapid and effective treatment of traumatic spinal cord injury using stem cell derived exosomes.

Similar Datasets

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