Osteoarthritis (OA) is an age-associated disorder affecting a large proportion of the elderly population. Current treatments for OA and cartilage degeneration are surprisingly limited to pain relief or total joint replacement resulting in huge medical costs. In this proposal, we propose to test a potential treatment for OA utilizing stem cells. It has been recently discovered that skin cells can be converted into pluripotent stem cells that resemble embryonic stem cells in their ability to give rise to various cell types. We propose to use these induced pluripotent stem cells to generate cells from patients themselves to effectively treat cartilage defects and avoid rejection upon transplantation. Recent reports have shown that cells from younger donors are more effective at treating cartilage defects than those from older donors. We plan to study young and old cells to identify the specific factors that can be employed to coax the stem cells towards young cartilage cells with a higher capacity for regeneration. We will test the stem cell derived young cartilage cells in rabbits and goats, for their capacity to repair cartilage defects created by surgery. A large animal model is essential to test cartilage regeneration as small animals like mice can undergo spontaneous repair hence do not faithfully recapitulate the conditions in humans. If successful, our proposed treatment will be a first disease-modifying treatment for cartilage regeneration and OA.
Statement of Benefit to California:
The establishment of CIRM has allowed California to be a front-runner in stem cell research. CIRM funds have helped create an intellectually stimulating scientific environment for stem cell innovation and applications with the potential to improve the quality of millions of patients’ lives. The funds invested by the state of California in multiple private and public institutions in stem cell research have also created significant job opportunities. This research proposal is in response to a call for early translational projects that aim to develop a cell-based therapy for a major unmet medical need. We propose a cell-based therapy for cartilage regeneration for repairing cartilage injuries and age-associated Osteoarthritis (OA). OA affects a large proportion of aged population in California and the rest of US. The only treatment options for OA to date are pain management and total joint replacement leading to a huge medical burden on the US economy. A potential early intervention therapy for cartilage regeneration would delay the progression of disease resulting in huge savings and improving the quality of many a patient' lives.The success of the proposed research could be a first disease modifying treatment for cartilage regeneration and would be a huge medical benefit in California as well as the rest of US.