Therapeutic Effect of BDNF-Overexpressing Human Neural Stem Cells (F3.BDNF) in a Contusion Model of Spinal Cord Injury in Rats.

Da-Jeong Chang,Hyunseung Lee,Seyoung Hwang,Hyun Sook Kim,Kwan Soo Hong,Seung-Hun Oh,Hwi-Young Cho,Jihwan Song,Dong Ah Shin,Nayeon Lee,Chunggab Choi,Young Wook Yoon

doi:10.3390/ijms22136970

Abstract

The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the thoracic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhibited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1- and iNOS-positive inflammatory cells as well as GFAP-positive astrocytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.

Highlights

Spinal cord injury (SCI) has very limited therapeutic options currently, despite its devastating pathology
Contusive SCI animal models were induced at the T11 level in SD rats, and 1 × 106 F3 cells (F3).BDNF cells or culture media were injected into the T9 at 7 days after injury
These results suggest that F3.BDNF cells play a crucial role in functional improvement by differentiating into functional neurons in the spinal cord and survive for an extended period of time in vivo

Summary

Introduction

Spinal cord injury (SCI) has very limited therapeutic options currently, despite its devastating pathology. Neural stem cells (NSCs) have the capacity to proliferate and have multipotent potential to differentiate into the major cell types in the central nervous system (CNS), including neurons, astrocytes, and oligodendrocytes. Transplantation of NSCs can replace the lost neural cells in the environment of injured spinal cord [5]. Transplantation of NSCs inhibits the activation and proliferation of T cells. They attenuated inflammation and reduced demyelination and axonal pathology, thereby improving the clinical severity in acute and chronic encephalomyelitis (EAE) [9]. Transplantation of NSCs can reduce inflammatory and gliosis reactions that contribute to demyelination, failure of axons, and cavitation following spinal cord injury [10,11,12]

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