Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats.

Abstract

Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by axonal/neuronal damage that may be caused by defective remyelination. Current therapies aim to slow the rate of degeneration, however there are no treatment options that can stop or reverse the myelin sheath damage. Bone marrow mesenchymal stem cells (MSCs) are a potential candidate for the cell implantation-targeted therapeutic strategies, but the pro-remyelination effects of MSCs when directly injected into a demyelinated cord lesion have been questioned. Neurotrophin-3 (NT-3) has been shown to serve a crucial role in the proliferation, differentiation and maturation of oligodendrocyte lineages. Here, we showed that implantation of NT-3 gene-modified MSCs via a recombinant adenoviral vector (Adv) into a region of ethidium bromide (EB)-induced demyelination in the spinal cord resulted in significant improvement of locomotor function and restoration of electrophysiological properties in rats. The morphological basis of this recovery was evidenced by robust myelin basic protein (MBP) expression and the extensive remyelination. AdvNT-3-MSC implants promote the endogenous remyelinating cells to participate directly in myelination, which was confirmed under light and electron microscopy. Our study suggested that genetically modified MSCs could be a potential therapeutic avenue for improving the efficacy of stem cell treatment for neurodegenerative diseases such as MS.

• Authors: Yu-Jiao Zhang, Wei Zhang, Cheng-Guang Lin, Ying Ding, Si-Fan Huang, Jin-Lang Wu, Yan Li, Hongxin Dong, Yuan-Shan Zeng
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 313 Issue 1-2 Pg. 64-74 (Feb 15 2012) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 21996274 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Myelin Basic Protein
• Neurotrophin 3

Topics

• Animals
• Demyelinating Diseases (genetics, pathology, surgery)
• Female
• Genetic Vectors (administration & dosage, genetics)
• Mesenchymal Stem Cell Transplantation (methods)
• Motor Activity (genetics)
• Myelin Basic Protein (biosynthesis)
• Myelin Sheath (metabolism, pathology, physiology)
• Neurotrophin 3 (administration & dosage, genetics)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (genetics)
• Spinal Cord Injuries (genetics, surgery)
• Thoracic Vertebrae