Intervertebral Disc Regeneration by Use of Autologous Mesenchymal Stem Cells

This dissertation, "Intervertebral Disc Regeneration by Use of Autologous Mesenchymal Stem Cells" by Grace, Ho, 何秀慧, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of the thesis entitled INTERVERTEBRAL DISC REGENERATION BY USE OF AUTOLOGOUS MESENCHYMAL STEM CELLS submitted by Ho Grace for the degree of Master of Philosophy at the University of Hong Kong in February 2005 Intervertebral disc degeneration is prevalent and is often associated with low back pain and reduced productivity. The etiology of this multi-factorial, age-related disease is not well defined. Disc degeneration is characterized by a reduction in cell density and a decreased in both the proteoglycan and water content. The consequent loss of shock- absorbing capacity results in its structural failure and back pain. The current treatments aim at alleviating the pain symptoms without targeting at the underlying problem. Mesenchymal stem cells (MSCs) are derived from the bone marrow and are capable of self-renewal and differentiation into multiple cell types of different lineages. Because of their unique characteristics, MSCs may be able to repopulate an aging disc population and halt disc degeneration when placed in a local niche that induce the differentiation of MSCs into disc-like cells and secrete disc-like extracellular matrix components. In a pilot study, I demonstrated the persistence of MSCs throughout the three disc compartments (the nucleus pulposus, the annulus fibrosus and the endplate) 12 weeks post-implantation. The MSCs intermingled with endogenous host cells, displaying similar cell morphology and surrounding extracellular matrix composition. To determine the effectiveness of MSCs in treating disc degeneration, a slowly progressive and reproducible animal model of disc degeneration was developed by puncturing the annulus fibrosus percutaneously. By semi-quantitative histological analysis, it was observed that MSCs were able to halt or retard degeneration of the more severely degenerated discs. The data further suggests that the regenerative potential of the MSCs is dependent on the severity of disc degeneration. Radiological analysis suggests that intervertebral disc height, an important consequence of disc degeneration, can be maintained simply by the insertion of a gelatin scaffold, whereas MSCs alone appears to be unable to secrete sufficient matrix to restore this height. Although the collagen-rich scaffold, by itself, was unable to reconstitute the extracellular matrix composition of the disc. Taken together, our experiments suggest that for the best regenerative potential, both cells and scaffold are likely required. An ideal scaffold should allow the restoration of the delicate balance of proteoglycan and collagen content, apart from providing mechanical properties and cell anchorage. Besides demonstrating that the direct MSCs therapy is highly feasible, these observations have profound impact on their application to treat intervertebral disc degeneration in human patients. The timing of stem cell therapy becomes very critical. The degree of the disc degeneration and the type of scaffolds that warrants the best results from the stem cell-based therapy would have to be further investigated. DOI: 10.5353/th_b3154161 Subjects: Stem cells Intervertebral disk - Diseases - Treatment