Dynamic Seeding versus Microinjection of Adipose-Derived Mesenchymal Stem Cells to Acellular Nerve Allograft Reconstructions.

Abstract

Functional recovery after acellular nerve allograft (ANA) reconstruction remains inferior to that after autologous nerve grafting, but improved outcomes have been demonstrated with the addition of adipose-derived mesenchymal stem cells (MSCs). Controversy exists regarding the optimal cell-delivery method to enhance ANA reconstructions. The authors investigated the functional recovery of ANAs after dynamic seeding versus microinjection of MSCs. Forty Lewis rats underwent reconstruction of a 10-mm sciatic nerve defect. Animals were divided into 4 groups: reversed autograft, ANA alone, dynamically seeded ANA, or ANA injected with MSCs. During the survival period, ultrasound measurements of the tibialis anterior muscle cross-sectional area were performed. At 12 weeks, functional recovery was evaluated using measurements of ankle contracture, compound muscle action potential, maximum isometric tetanic force, muscle mass, histomorphometry, and immunofluorescence. The dynamic seeding and microinjection groups demonstrated higher cross-sectional tibialis anterior muscle area recovery than autografts and ANAs alone at week 8 and weeks 4 and 8, respectively. The ankle contracture and compound muscle action potential amplitude recovery were superior in autografts and both seeding methods compared with ANAs alone. The microinjection group demonstrated significantly higher isometric tetanic force, muscle mass, and number of axons compared with ANAs alone. Both seeding methods showed higher CD34 densities compared with ANAs alone. No significant differences between dynamic seeding and microinjection were observed in functional or histologic outcomes. The addition of MSCs to ANAs demonstrated earlier motor regeneration compared with autografts and ANAs alone. Both seeding methods improved functional outcomes in the rat sciatic nerve defect model.