Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in the rat

Abstract

Bone marrow stromal cells (BMSCs) have been studied as effective transplants for the treatment of spinal cord injury (SCI). Our previous study showed that BMSCs infused into the cerebrospinal fluid (CSF) exhibited distinct effects on the recovery of acute SCI. The present study examined the effects of BMSCs in sub-acute SCI (2 weeks post-injury) by transplanting them directly into the lesion. The spinal cord was crush-injured at the Th8-9 level in rats, and 2 weeks later, cultured BMSCs (5 × 10 5) derived from GFP-transgenic rats of the same strain were transplanted into the lesion. Tissue repair and nerve regeneration were examined by immunohistochemistry and electron microscopy. GFP-labeled BMSCs survived as cell assemblies in the spinal cord for 1-2 weeks after transplantation. The dorsal side of BMSC assemblies in the spinal cord usually showed an expanded GFAP-negative, astrocyte-devoid area, in which extracellular matrices including collagen fibrils were deposited. Numerous regenerating axons associated with Schwann cells grew out through such astrocyte-devoid extracellular matrices. Ascending (CGRP-containing) and descending (5HT- and TH-containing) axons were included in these regenerating axons. Regenerated axons were myelinated by Schwann cells beyond 2 weeks post-transplantation. Cavity formation was reduced in the cell transplantation group. Locomotory behavior assessed by the BBB scale improved to 9.8 points in the cell transplantation group, while it was to 5.5-5.7 in the control. BMSC transplantation into lesions of advanced SCI has markedly beneficial effects on tissue repair and axonal outgrowth, leading to improved locomotion in rats.