What do skin and cartilage have in common? It depends on who you ask. Dr. Veronique Lefebvre, a researcher at Cleveland Clinic Lerner Research Institute, is currently working on a 2016 foundation-funded project called “Quality-by-Design approach to create articular cartilage from pluripotency” that connects the dots between skin and cartilage. Dr. Lefebvre and her team are developing a protocol that starts with skin cells and ends with knee cartilage.
The team starts with stem cells collected from the skin. The stem cells are then ’re‑programmed’ to become induced pluripotent stem (IPS) cells. IPS cells can be converted into any kind of cell needed. Dr. Lefebvre told us they can start with any cell in the body to create stem cells, but skin cells are the easiest source to use.
The team is also studying proteins, called transcription factors, and other growth factors (like hormones) that control cell identity and activity. They tested different the combinations of transcription and growth factors, as well as when each factor comes into play, to create a protocol that will turn the IPS cells into knee chondrocytes (cartilage-making cells).
“Many research teams have been working on this,” explains Dr. Lefebvre. “So far, none have been able to perfect the process. To create the best protocol, you must start with a specific type of cell (in this case, skin stem cells) and turn them into a specific target cell (knee chondrocyte cells). The reason we start and end with specific types of cells is because each type of cell is unique.”
Many don’t know that knee cartilage cells are different from hip cartilage cells. Just as with skin, some types of cartilage are thicker based on how much cartilage is needed to protect an area of bone. Bones that bear more weight or endure more pressure during normal activities require more cartilage for protection. The body provides cues as to what type of cell should grow based on its location.
“By developing a specific type of cartilage for a specific area of the body, we will have the best chance for the new cells to grow into healthy tissue,” Dr. Lefebvre said. “So far, we’ve had very promising data.”
The goal of this study is to find a way to consistently produce a specific type of cartilage. The next steps for Dr. Lefebvre and her team will be to identify the right scaffold to grow the cells on so they can eventually implant the new cells into a subject. Many steps remain before the cartilage-creating protocol is ready to be tested in humans. However, Dr. Lefebvre and her team are hopeful that they may be able to begin human trials in 2019.
“This will offer a life-changing treatment for arthritis patients,” she said. “Our current treatment options are extremes: you either take an anti-inflammatory drug or you have joint replacement. You may be pain-free as long as you take a pill, but it doesn’t solve the problem. By replacing or repairing cartilage, we may offer a chance to restore joint normalcy.”
Dr. Lefebvre and her team work at the Cleveland Clinic Foundation in Cleveland, Ohio. She has been awarded Arthritis Foundation funding for three cartilage-related projects, including her current project. She received an Arthritis Foundation Investigator grant while working at the University of Texas from 1996-1999 and an Innovative Research grant while working at the Cleveland Clinic Foundation from 2003-2005.