Year 3

Articular cartilage injuries and degeneration eventually lead to osteoarthritis, costing $65B per year and affecting over 25% of adults over the age of 65. This Development Candidate Feasibility (DCF) Award seeks to address cartilage defects classified by the International Cartilage Repair Society (ICRS) as grades II-IV with the intent of halting the progression of cartilage damage before it creates arthritic changes in joint compartments. The therapy would begin with a biopsy of the patient’s own skin to harvest dermis isolated, adult stem cells (DIAS cells), which will undergo processing to yield neocartilage. This neocartilage will then be implanted into the patient’s joint to restore or improve mobility. The project objective has not changed from previous progress reports, though new milestones have been proposed during this reporting period and approved by CIRM, as described below.

Milestone 1 was completed and, after reporting of preliminary data from Milestone 2, a prior approval request was submitted with a description of critical path experiments to amend the milestones, and a no cost extension was also submitted. These have been approved by CIRM. The new, remaining milestones to be completed consist of: three studies in the athymic mice using human DIAS neocartilage generated from foreskin, breast skin, and abdominal skin, from multiple donors (Milestone 2); a study to apply aggregate redifferentiation to human DIAS cells to yield cells with a chondrogenic phenotype (Milestone 3), and the rabbit study as initially approved, using human DIAS cells and with an abridged timeline (Milestone 4).

As proposed and approved, the three athymic mouse studies are currently in progress. The mouse portion of the first study, using breast skin-derived DIAS cells, has been completed. Studies using abdominal skin- and foreskin-derived DIAS cells are on track for completion in March and April, 2016. The aggregation redifferentiation study is currently ongoing, and neocartilage constructs have yet to be generated. The rabbit study is under planning for its immunosuppression component. Additionally, a paper was published during this reporting period to disseminate scientific findings to the public.