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.”
很多人不知道膝关节软骨细胞不同于髋关节软骨细胞。就像皮肤一样，某些类型的软骨会根据保护骨骼区域所需的软骨量而变厚。在正常活动中承受更多重量或承受更多压力的骨骼需要更多的软骨来保护。身体会根据细胞的位置提供生长何种类型细胞的线索。
“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.
她说:“这将为关节炎患者提供一种改变生活的治疗方法。”“我们目前的治疗选择都是极端的:要么服用消炎药，要么进行关节置换。只要你吃了一片药，你可能就没有疼痛了，但这并不能解决问题。通过更换或修复软骨，我们可以提供一个恢复关节正常的机会。”
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.