Combined Wharton's jelly derived mesenchymal stem cells and nerve guidance conduit: A potential promising therapy for peripheral nerve injuries

Abstract

Background: Peripheral nerve injuries represent a clinical problem with insufficient or unsatisfactory treatment options. Functional outcome with nerve guidance conduits was unsatisfactory in nerve defects with increased gap size. So, cell therapy may benefit as a tool for optimizing the regeneration process. The aim of the present study was to evaluate the impact of combination of cell therapy and nerve guidance conduits on the nerve regeneration and on the expression of the factors aiding the regeneration in a rat model of sciatic nerve injury.

Methods and results: Sixty Wistar rats were randomly divided into four groups: Group I: normal control group; Group II: sciatic nerve injury (SNI) with a 10mm long sciatic nerve gap; Group III: SNI with using a nerve conduit (NC) for nerve gap bridging; and Group IV: SNI with using a NC associated with Wharton's jelly derived mesenchymal stem cells (WJ-MSCs). The results showed that the combination therapy NC+WJ-MSCs caused much better beneficial effects than NC alone evidenced by increasing sciatic nerve index and pin-prick score. The histopathological analysis found that the use of the NC combined with WJ[HYPHEN]MSCs resulted in a structure of the sciatic nerve comparable to the normal one with better nerve regeneration when compared with NC only. There was no differentiation of WJ-MSCs into nerve structure. Lastly, there was an upregulation of expression for netrin-1, ninjurin, BDNF, GDNF, VEGF and angiopoitin-1 rat genes in NC+WJ-MSCs group than NC alone.

Conclusion: The addition of WJ-MSCs to the nerve guidance conduits seems to bring significant advantage for nerve regeneration, basically by increasing the expression of neurotrophic and angiogenic factors establishing more favorable environment for nerve regeneration.

Keywords: Angiogenic factors; Mesenchymal stem cells; Nerve conduit; Nerve regeneration; Neurotrophic factors; Peripheral nerve; WJ-MSCs.