Brain Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor-Transfected Bone Mesenchymal Stem Cells for the Repair of Periphery Nerve Injury.

Qiang Zhang,Céline Huselstein,Xiaohua He,Ping Wu,Zan Tong,Qifa Ye,Yinping Li,Feixiang Chen,Yun Chen,Yanan Zhao

doi:10.3389/fbioe.2020.00874

Abstract

Peripheral nerve injury is a common clinical neurological disease. In our previous study, highly oriented poly (L-lactic acid) (PLLA)/soy protein isolate (SPI) nanofiber nerve conduits were constructed and exhibited a certain repair capacity for peripheral nerve injury. In order to further improve their nerve repairing efficiency, the bone mesenchymal stem cells (BMSCs) overexpressing brain derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were introduced into the conduits as seed cells and then were used to repair the 10-mm sciatic nerve defects in rats. The nerve repair efficiency of the functional nerve conduits was evaluated by gait experiment, electrophysiological test, and a series of assays such as hemotoxylin-eosin (HE) staining, immunofluorescence staining, toluidine blue (TB) staining, transmission electron microscopy (TEM) observation of regenerated nerve and Masson’s trichrome staining of gastrocnemius muscle. The results showed that the conduits containing BMSCs overexpressing BDNF and GDNF double-factors group had better nerve repairing efficiency than blank BMSCs and single BDNF or GDNF factor groups, and superior to autografts group in some aspects. These data demonstrated that BDNF and GDNF produced by BMSCs could synergistically promote peripheral nerve repair. This study shed a new light on the conduits and stem cells-based peripheral nerve repair.

Highlights

Peripheral nerve injury (PNI) is a critical issue in the field of regenerative medicine (Wang et al, 2018; Li et al, 2020)
The surface markers CD11b, CD45, CD29, and CD90 of bone mesenchymal stem cells (BMSCs) were identified by flow cytometry, and the results are shown in Supplementary Figures S1C– F
The positive expression of CD29 was more than 99%, the positive expression of CD90 was more than 95%, while the positive rate of CD11b and CD45 was less than 1%, indicating that the purity of BMSCs was more than 95%

Summary

Introduction

Peripheral nerve injury (PNI) is a critical issue in the field of regenerative medicine (Wang et al, 2018; Li et al, 2020). Accelerating axonal regeneration and improving functional recovery after PNI is a clinical dilemma and a basic medical challenge (Li et al, 2019; Sayad-Fathi et al, 2019). The gold standard of long nerve regeneration is autograft (Yi et al, 2018; Vijayavenkataraman, 2020). Autograft requires sacrifice of a functional nerve, which may result in donor nerve sensory loss and neuropathic pain (Guo et al, 2018; Wu et al, 2020). The use of nerve guide conduits could avoid these problems (Chrzaszcz et al, 2018; Chen et al, 2019; Vijayavenkataraman et al, 2019). The reported nerve conduits could not fully meet the demands for quick and effective nerve repair (Carvalho et al, 2019; Riccio et al, 2019)

Results

Discussion

Conclusion