Autologous Marrow-Derived Stem Cell-Seeded Gene-Supplemented Collagen Scaffolds for Spinal Cord Regeneration as a Treatment for Paralysis
The long-term objective of this research is to develop a device for treating spinal cord injury and thereby curing selected forms of paralysis.
Every year an estimated 15,000 persons suffer spinal cord injury. An estimated 500,000 people are currently paralyzed from the waist or neck down, and one million are estimated to have spinal cord-associated deficiencies with less severe implications. The restoration of even a small amount of function by axon regeneration and reconnection would lead to a significant improvement in the quality of life.
Current clinical treatments for spinal cord injury are successful in minimizing the severity of injury by suppressing the inflammatory response and secondary damage at the injury site but do not facilitate the repair or growth of injured nerve fibers. There is a compelling need for therapies that will not only minimize secondary damage but also restore function that has been lost through facilitation of the growth of axons across the injury gap.
Previous studies performed in collaboration with Professor I.V. Yannas of MIT demonstrated that a porous, absorbable, collagen-glycosaminoglycan matrix-filled collagen tube was capable of promoting the growth of nerve fibers (axons) when implanted into a gap injury in the rat peripheral nerve. The device outperforms the nerve autograft "gold standard" with respect to the axonal structure at the termini of the tibial and peroneal branches of a rat sciatic nerve in which the device has been implanted to bridge a 10-mm gap. The electrophysiological properties of the nerve regenerated through the collagen device also are nearer to normal when compared to an autograft. We have completed preliminary studies in which we evaluated the ability of collagen-glycosaminoglycan matrices to support the regrowth of spinal cord axons. Samples of matrix identical to those that promoted maximal peripheral nerve were implanted into gap injuries in the spinal cords of adult rats. Nerve fibers from the spinal cord and spinal roots were able to grow into collagen-glycosaminoglycan matrices 30 days after implantation. However, the regeneration was well sub-optimal with respect to the number and diameter of the axons. The specific aims of the ongoing study are to test the hypothesis that seeding of the collagen-glycosaminoglycan matrices with bone marrow-derived mesenchymal stem cells will facilitate the regeneration process using our rat model. Moreover, we will incorporate genes encoding for selected nerve growth factors into the collagen scaffold.
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