The Effect of Local Exosomes, Stem Cells and Tacrolimus on Neurite Extension
Year: 2023
Type: article
Abstract: BACKGROUND: Reconstruction of nerve injuries using nerve allograft still results in inferior regeneration and motor outcomes to the nerve autograft. Nerve regeneration can be enhanced by modulating the local microenvironment of the nerve reconstruction site. The aim of this study was to investigate the combined effect of local delivery of Purified Exosome Product (PEP), mesenchymal stem cells (MSCs) and Tacrolimus (FK506) alone and combined on nerve regeneration. METHODS: A three-dimensional in vitro compartmented cell culture system was used to evaluate regenerating neurites from a rat neonatal dorsal root ganglion into the adjacent nerve. Decellularized allografts were augmented with local application of (i) MSCs, (ii) PEP (5%), (iii) FK506 (100 ng/mL), (iv) combined PEP and FK506, and (v) combined MSC and FK506 (N=9/group). Outcomes were compared to untreated autografts and allografts. After 48 hours, constructs were stained against Neurofilament-160 to measure neurite extension as a measure of nerve regeneration, and CD90-DAPI to confirm stem cell characterization. RESULTS: Stem cell viability was confirmed in all MSC-treated grafts using CD90-DAPI staining. Treatment with PEP, PEP and FK506, and MSCs and FK506 significantly improved outcomes of untreated allografts (p<0.0001, p<0.0001, p<0.001) and were found comparable to the untreated autograft (p>0.99, p>0.99, 0.99). Combined treatments of PEP and FK506 and MSCs and FK506 were found comparable (p>0.99). Combined MSCs and FK506 treatment was found superior to MSCs alone (p<0.02). CONCLUSION: PEP treatment alone, PEP combined with FK506 and MSCs combined with FK506 resulted in a significant neurite extension, and was found comparable to the current gold standard, the autograft. These results suggest that the neuroregenerative effect of PEP is similar to MSCs. PEP could overcome the limitations of harvesting, culturing and seeding of stem cells, making this more translatable to clinical care. In vivo animal models are needed to further investigate the effect of PEP alone and combined with FK506 in nerve regeneration.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W4387738647