Peripheral nerve regeneration after experimental section in ovine radial and tibial nerves using synthetic nerve grafts, including expanded bone marrow mesenchymal cells: morphological and neurophysiological results

ABSTRACTThe standard treatment of peripherical nerve injuries with substance gap is to introduce the nerve free extremes in a biodegradable tube which, as a biocamera, allows the continuity of the nerve, promote the neuroconduction and save the lesion from the surrounding fibrosis. However, this procedure has not any direct effect on the neuroregeneration nor to resolve high severe lesions.The mesenchymal stem cells (MSC) can derivate “in vitro“ in different lineages, including Schwann cells. Different studies have shown MSC can promote the nerve regeneration in rodents, dogs and primates. Moving to the human clinical application requires the procedure standardization, including the optimal cell dose which we have to use.In the sheep model animal we performed a study of 1 cm. nerve section-ressection and repair with a Neurolac™ biocamera, in whose gap we applied between 30 to 50×106 MSC from cancellous bone, all of them selected and cultured with GMP procedures. The results were compared with controls (saline serum ± platelet-rich plasma).We used radial nerve (sensitive) and tibial nerve (motor) from 7 sheep. In the first step we performed the surgical lesion and bone marrow aspiration, and in 3 weeks we performed the surgical repair. 3 sheep were sacrificed in 3 months, and 4 sheep in 6 months. In all surgeries we performed a neurophysiological register.When we obtained the tissue samples, we performed an histological, immunohistiquimical and morphometrical study. The recovery percentage was defined comparing the axonal density from the proximal and distal lesion margins.The 3 months samples results were wrong. In 6 months samples results we observed a significative myelined nervous fibers and conduction increasing, in front of controls, both radial and tibial nerves. These results suggest the MSC application in biodegradable scaffold in nerve injuries promotes good results in terms of regeneration and functional recovery.