Cell-enrichment with olfactory ensheathing cells has limited local extra beneficial effects on nerve regeneration supported by the nerve guide Perimaix

Abstract

The reconstruction of peripheral nerve injuries is clinically challenging, and today, the autologous nerve transplantation is still considered as the only gold standard remedy for nerve lesions where a direct nerve coaptation is not possible. Nevertheless, the functional merits of many biomaterials have been tested as potential substitutes for the autologous nerve transplant. One of the strategies that have been pursued is the combination of bioengineered nerve guides with cellular enrichment. In this present study, we combined the previously evaluated collagen-based and microstructured nerve guide Perimaix with olfactory ensheathing cell enrichment. Rat sciatic nerve defects of 20 mm were either bridged by a cell-seeded or nonseeded nerve guide or an autologous nerve transplant. Animals were monitored for 12 weeks for structural and functional parameters. Seeded cells survived on Perimaix, and following implantation aligned along the microstructured Perimaix framework. Axonal densities within the cell-seeded nerve guides were higher than in the nonseeded nerve guides and were comparable to the autograft. Additionally, cell-seeding had local beneficial effects on myelination within the nerve guide, as myelin sheath thickness was enhanced when compared with the empty scaffold. Nevertheless, for bridging the nerve gap of 20 mm, both the cell-seeded as well as nonseeded scaffolds were equally efficient regarding the functional outcome, which did not differ between the autograft, seeded or nonseeded groups. Our data demonstrate that olfactory ensheathing cell enrichment has local effects on nerve regeneration in combination with the Perimaix nerve guide. Surprisingly, for traversing the lesion gap, additional cell-seeding is not crucial.

A Systematic Review of the Effectiveness of Cell-Based Therapy in Repairing Peripheral Nerve Gap Defects

“…However, the results are less successful than autologous nerve grafting, the gold standard of nerve repair, which implies that cell therapy can assist nerve regeneration but it cannot replace nerve grafting altogether. It is noteworthy that a few studies have also reported that cell therapy is beneficial only for boosting nerve regeneration at the very beginning of the repair process and it does not necessarily make any difference afterward [50]. Hence, the possibility of stem cells inducing a transient positive effect on nerve regeneration should not be overlooked.…”

Role of exosomes in the pathogenesis, diagnosis, and treatment of central nervous system diseases

“…[ 133 ]. Olfactory ensheathing cells (OECs) have the function of promoting nerve regeneration, but their application is limited because of the oxygen-deficient environment at the injury site [ 134 ]. Zhang et al showed that exosomal treatment significantly promoted the survival and migration of OECs in hypoxic conditions, and effectively increased brain-derived neurotrophic factor gene expression, protein levels and secretion [ 135 ].…”

The Effect of Schwann Cells/Schwann Cell-Like Cells on Cell Therapy for Peripheral Neuropathy

“…They also exhibit great potentials for nerve repair in peripheral nerve injury-induced neuropathy ( Radtke et al, 2009b , 2011 ; Radtke and Kocsis, 2012 , 2014 ). Olfactory bulb ensheathing cells from mouse ( Goulart et al, 2016 ) and rat mediate improvements in axonal regeneration, myelination and sciatic nerve functional recovery in mouse sciatic nerve transection with a 3 mm gap, and in rat sciatic nerve transection with a 15 or 12 mm gap ( Verdú et al, 1999 ; You et al, 2011 ; Zhang et al, 2019 ), and 20 mm gap ( Guérout et al, 2011 ; Boecker et al, 2018 ), and with microsurgical nerve repair ( Radtke et al, 2009a ) and in rat sciatic nerve crush lesion ( Dombrowski et al, 2006 ), as well as in rat facial nerve transection with a 5 mm gap ( Guntinas-Lichius et al, 2001 ). As well, transplantation of olfactory mucosa significantly increases the accuracy of target reinnervation and accelerates the vibrissae movements ( Guntinas-Lichius et al, 2002 ).…”