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Principal Investigator: Dr. Alan Nixon
Contact Information: E-mail: ajn1@cornell.edu - Phone: 607-253-3224
Sponsor: American Quarter Horse Association
Grant Number: N/A
Title: Use of Growth Factor Gene Enhanced Adult Stem Cells for Cartilage Repair
Annual Direct Cost: $54,405
Project Period: 10/01/05-09/30/07
This research proposal will develop methods to enhance the ability of stem cells to repair diseased joints. The fundamental goal is to use stem-cell based cartilage resurfacing to lessen arthritis and delayed return to performance in athletes. Stem cells are the pluripotent cells that respond to the body's call for repair of musculoskeletal tissues such as muscle, tendon, bone, and cartilage. By stimulating stem cell transformation into cartilage cells, joint surfaces may undergo a more effective cartilage repair, and the debilitating and occasionally life threatening sequelae of arthritis and stress induced joint breakdown injury may be averted. Previous studies in the investigator's laboratory indicate that a small bioactive peptide, insulin-like growth factor-I (IGF-I), drives stem ceils toward the cartilage cell line and pumps the biosynthetic capacity of equine stem cells. This research proposal seeks to develop and test new growth factor genes that may enhance stem cell transformation to cartilage cells, and to evaluate the impact of insertion of the IGF-I gene into stem cells, prior to their transfer from lab cultures back into significant articular defects. We have shown that various members of the Transforming Growth Factor-beta (TGF-ß) family can drive stem cells toward cartilage lines when applied as proteins, and we hypothesize that the genes for these same TGF-ß members may be more effective at long-term cell differentiation. Additionally we have demonstrated that IGF-I can direct stem cells to contribute more to intrinsic cartilage healing. Growth factors perform these functions in natural healing mechanisms, and it is our second hypothesis that additional IGF-I may not only hasten the transformation of stem cells to cartilage cells after transfer into cartilage injuries, but drive the synthesis of new cartilage components by these transformed cells. Indeed, IGF-I causes the cartilage end-plate of adolescent bones to grow and it seems logical that a recapitulation of this mechanism should help joint cartilage to repair. Since IGF-I proteins are quickly lost from the joint, this grant will study gene therapy approaches to insert the IGF gene directly into the stem cells destined for transplantation, so that they become their own "microfactory" for IGF-I production. The dual impact of stem cells that are extensively transformed toward new cartilage cells at the time of implant (by TGF-ß) and also contain active stimulatory genes that promote deposition of new cartilage structure is an elegant means to drive a significant improvement in cartilage repair and arthritis stabilization. The long-range goal is to provide a ready source of cartilage-like cells derived from the animals own body, to insert stimulatory genes, and to transfer these cells to acutely damaged joints, where they will improve cartilage healing to the point of preventing arthritis and other secondary breakdown injuries.
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