Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model

Qinfeng Wu,Jing Zang,Chuanming Dong,Zhangjie Li,Chen Xu,Zhangwei Wang,Guangyu Shen,Haoming Li,Jiaqi Cheng,Qinghua Wang,Xiangzhe Li,Yujia Gong

doi:10.1038/s41419-018-0847-8

Abstract

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1β were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

Highlights

Spinal cord injury (SCI), leading to permanent sensory and motor function deficits below the lesion level due to the lack of regeneration of the damaged axons, and has been remained as one of the hot clinical challenges[1,2]
Some drawbacks shadowed with neural stem cells (NSCs): adult NSCs were not available for autologous cell transplant, fetal-derived NSCs had ethical concerns, and a previous study reported a boy with ataxia telangiectasia (AT), who received human fetal neural stem cell transplantation, while he suffered from brain tumor[9]
The mesenchymal stem cells (MenSCs) can be induced into osteoblast cells confirmed by Alizarin red S staining and adipocytes confirmed by Oil Red O staining (Fig. 1c, d)

Summary

Introduction

Spinal cord injury (SCI), leading to permanent sensory and motor function deficits below the lesion level due to the lack of regeneration of the damaged axons, and has been remained as one of the hot clinical challenges[1,2]. The most promising stem cell is neural stem cells (NSCs), because NSCs harbor a certain ability to differentiate into neural and glial cells when are transplanted in the site of SCI8. Mesenchymal stem cells (MSCs) are multipotent adult stem cells which can differentiate into multiple cell types[10]. Transplantation of MSCs into the injured rat spinal cord promoted tissue preservation by directly replacing the damaged cells, decreasing the cyst and injury area, stimulating axonal sprouting, producing neurotrophic factors, as well as inhibiting inflammatory cytokines[11,12]

Methods

Results

Conclusion