Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

Hui Liu,Yongjia Zhu,Li Zheng,Fuben Xu,Huayu Wu,Peizhen Lv,Jinmin Zhao,Kun Zhang

doi:10.1038/srep39869

Abstract

Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

Highlights

Peripheral nerve injuries caused by accidental trauma, acute compression, iatrogenic injury or hematomas are cosmopolitan health concerns, which may lead to the disruption of myelin sheaths and axons[1]
SDS, structure shown in Fig. 1A), a phenylpropanoid glycoside extracted from Rhodiola rosea L, a popular plant in traditional medicine in Eastern Europe and Asia, has been reported to have diverse pharmacological properties including antiviral, anticancer, hepatoprotective, antidiabetic and antioxidative effects[17,18,19,20,21]
We intended to investigate the neuroprotective effects of SDS on engineered nerve constructed by RSC 96 and PLGA in vitro and further the possibility of combining SDS therapy with tissue engineering strategy on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection

Summary

Results

Effects of SDS on RSC 96 in vitro. Preliminary drug screening and cell cytotoxicity assay. At 12 weeks post-operation, both SDS and PLGA/SCs group showed significantly better recovery of regenerated nerve compared to control (P < 0.05). The present study was intended to demonstrate the effect of SDS on RSC 96 cultured on PLGA film in vitro and further the combinational therapy on nerve regeneration after nerve transection injury in rats. Cell proliferation and growth were significantly enhanced in 0.2 mM SDS group compared with untreated counterparts, as evidenced by preliminary drug screening (Fig. 1B), cell cytotoxicity assay (Fig. 1C), cell viability assay (Fig. 1E) and morphological evaluation (Fig. 2). In correspondence with the immunohistochemical staining, the upregulated expression of BDNF, GDNF and CNTF (Fig. 3D) indicated the positive effect of SDS on SCs in vitro.

Materials and Methods

Gene GDNF BDNF CNTF GAPDH

Author Contributions

Additional Information