In Vivo Functional Outcomes of Stem Cell Delivery Methods to Acellular Nerve Allografts
Year: 2022
Type: article
Abstract: BACKGROUND: Different cell delivery methods have been described to supplement biological scaffolds, such as acellular nerve allografts (ANAs). We sought to investigate the functional motor recovery of ANAs after dynamic seeding versus microinjection of adipose-derived mesenchymal stem cells (MSCs). METHODS: Forty Lewis rats underwent reconstruction of a 10-mm sciatic nerve defect. Animals were divided into four experimental groups (n = 10/group): I) autograft, II) ANA, III) ANA dynamically seeded with MSCs, and IV) ANA injected with MSCs. In group III, ANAs were dynamically seeded with1x10ˆ6 MSCs on a bioreactor for 12-24 hours prior to surgery. ANAs in group IV were longitudinally injected with 1x10ˆ6 MSCs in 10 μL of culture medium over the entire course of the nerve graft. During the survival period, the tibialis anterior (TA) muscle cross-sectional area was measured using ultrasound imaging. In non-survival procedures at 12 weeks, measurements of ankle contracture, compound muscle action potential (CMAP), isometric tetanic force (ITF), and wet muscle weight (MW) were determined. All results were expressed as a percentage of the contralateral non-operated side. RESULTS: TA cross-sectional area recovery was significantly higher in groups III and IV compared to groups I and II at week 8. Group IV also showed significantly higher recovery rates than group I and II at week 4. The ankle contracture and CMAP amplitude were inferior in ANAs alone compared to all other groups. Group IV demonstrated significantly higher ITF and MW compared to ANAs alone. No significant differences were observed between ANAs dynamically seeded with MSCs and ANAs injected with MSCs. CONCLUSION: Addition of MSCs to ANAs demonstrated earlier regeneration compared to ANAs alone and autografts and were demonstrated as early as postoperative week 4. Both methods of seeding improved functional outcomes. The method chosen for human translation must be technically feasible, reproducible, and timely.
Institution: Mayo Clinic
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,195
OpenAlex ID: W4385296900
