Mesenchymal stem cells in the treatment of spinal cord injuries: A review

Abstract

With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

Keywords: Adipose tissue derived mesenchymal stem cells; Bone marrow stromal cells; Mesenchymal stem cells; Spinal cord injury; Umbilical cord derived mesenchymal stem cells.

Figures

Figure 1

Transmission electron micrographs of shiverer mice brain showing thin and fragmented myelin around the axons in control and WI-38- implanted mice. In contrast, human umbilical cord blood-derived mesenchymal stem cells-treated shiverer brains showing myelin with several layers. Images are representatives of the several sections obtained from 3 different animals (n = 3). Scale bar = 33000. Stem Cells Dev 2011; 20: 881-891.

Figure 2

Microarray analysis of apoptotic genes after spinal cord injury. Total RNA was extracted from sham control, 3-wk post-spinal cord injury (SCI), and 3-wk post-SCI plus human umbilical cord blood-derived mesenchymal stem cells (hUCBSC)-treated tissues, reverse-transcribed, and the corresponding cDNA was loaded into a 96-well plate. In each group, RNA from at least three different animals was pooled together. A and C: Representative scatter plots show the validity of the experiment and the expression level of each gene in the control vs injured and injured vs hUCBSC-treated samples; B and D: These 3D profile graphs show the fold difference in expression of each gene between sham control vs injured and injured vs hUCBSC-treated samples. These experiments were performed in duplicate (hUCBSC, human umbilical cord blood-derived mesenchymal stem cells; SCI, spinal cord injury). J Neurotrauma 2009; 26: 2057-2069.

Figure 3

Reduction of inflammation in human umbilical cord blood-derived mesenchymal stem cell-treated spinal cords of rats. Immunohistochemical comparison of control, injured (21 d after spinal cord injury) and human umbilical cord blood-derived mesenchymal stem cells-treated spinal cord sections was performed to analyze the expression of reactive astrocytes at the site of injury. GFAP immunoreactivity is more evident and is localized at the lesion epicenter in the injured spinal cords. Astrogliosis is reduced in human umbilical cord blood-derived mesenchymal stem cells-treated sections. SI: Site of injury. Neurobiol Dis 2009; 36: 200-212.