Cartilage degeneration resulting from injuries or wear-and-tear leads to osteoarthritis, which impacts millions and costs in excess of $65B per annum. No long-term solutions exist for cartilage degeneration, but cellular therapies hold promise toward replacing degenerated cartilage with healthy tissue. This Development Candidate Feasibility Award is a first step toward the overall goal of developing a cell-based cartilage repair therapy using stem cells derived from the skin. The therapy would consist of using a skin biopsy 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.
Work during this progress report period has been divided into project preparation and scientific progress. Project preparation includes setting up facilities and approvals for work with human DIAS cells, identifying sources and acquiring human skin for DIAS cell isolation, and hiring and training personnel. Scientific progress includes a publication on co-cultures using stem cells, work on culturing larger numbers of cells using low oxygen tension, comparing stem cells from human skin of different anatomical locations, and gaining an understanding of the niches where skin stem cells may reside.
The project now has a consistent source of human dermis tissue from which stem cells can be isolated. This includes skin containing hair follicles and also skin without follicles. Spherical culture of human skin-derived stem cells has been performed. It was found that directing stem cells into cells that make cartilaginous matrix can be more efficacious if done under low oxygen tension. Since much of the prior work on directing stem cells from the skin to form neocartilage has been done using animal-derived stem cells, in the next project period neocartilage will be formed using human stem cells instead. Technologies developed using animal models can thus be translated toward human use.