Co-transplantation of Epidermal Neural Crest Stem Cells and Olfactory Ensheathing Cells Repairs Sciatic Nerve Defects in Rats.

Lu Zhang,Bingcang Li,Zhifang Dong,Bin Liu

doi:10.3389/fncel.2019.00253

Abstract

Cell-based therapy is an alternative strategy to improve outcomes of peripheral nerve injury (PNI). Epidermal neural crest stem cell (EPI-NCSC) is obtained from autologous tissue without immunological rejection, which could expand quickly in vitro and is suitable candidate for cell-based therapy. Olfactory ensheathing cell (OEC) could secrete multiple neurotrophic factors (NTFs), which is often used to repair PNI individually. However, whether the combination of EPI-NCSC and OEC have better effects on PNI repair remains unclear. Here we use EPI-NCSC and OEC co-transplantation in a rat sciatic nerve defect model to ascertain the effects and potential mechanisms of cells co-transplantation on PNI. The effect of EPI-NCSC and OEC co-transplantation on PNI is assessed by using a combination of immunohistochemistry (IHC), electrophysiological recording and neural function test. Co-transplantation of EPI-NCSC and OEC exerts a beneficial effect upon PNI such as better organized structure, nerve function recovery, and lower motoneuron apoptosis. IHC and enzyme-linked immuno sorbent assay (ELISA) further demonstrate that cells co-transplantation may improve PNI via the expression of brain derived growth factor (BDNF) and nerve growth factor (NGF) up-regulated by EPI-NCSC and OEC synergistically. Eventually, the results from this study reveal that EPI-NCSC and OEC co-transplantation effectively repairs PNI through enhancing the level of BDNF and NGF, indicating that cells co-transplantation may serve as a fruitful avenue for PNI in clinic treatment.

Highlights

Peripheral nerve injury continues to be a major challenge in reconstructive neurosurgery
Epidermal neural crest stem cells migrated from the bulge of hair follicles of GFP-rats and subcultured for 3 passages (P3), and the cells displayed a spindle-like shape (Green, Figure 1A) with green fluorescent protein (GFP)
The results showed that the amplitude of compound muscle action potentials (cMAPs) was much bigger in the EPI-NCSC, olfactory ensheathing cells (OECs), and EPI-NCSC+OEC groups than that recorded in the DMEM/F12 group (∗∗∗P < 0.001; Figure 4B)

Summary

Introduction

Peripheral nerve injury continues to be a major challenge in reconstructive neurosurgery. NTE has been shown to satisfy this need. It is typically comprised of a neural scaffold with incorporated biochemical cues. Among a large body of scaffold biomaterials, Poly(lactic-co-glycolic acid) (PLGA) (Bini et al, 2004), comprised of Polylactide (PLA) and Polyglycolide (PGA), shows excellent neural affinity and biocompatibility with cells. PLGA can be used to control the release of inosine, NGF and insulin-like growth factor (IGF), and combine to seed cells such as Schwann cells, bone marrow stromal cells (BMSCs) or neural stem cells (NSCs), or can be processed into a graft for guiding peripheral nerve regeneration

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Conclusion