Koepke, Lauren, 2017-2018

Lauren Koepke
Lauren
Koepke

"Characterization and Manipulation of the Human Skeletal Stem Cell Lineage in Response to Microfracture Surgery "

Host Mentors: Charles K.F. Chan , Michael T. Longaker
Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford Immunology Stanford School of Medicine

Osteoarthritis (OA) is a chronic disease characterized by a progressive loss of hyaline cartilage, leading to restricted movement and painful joints. Due to a lack of vasculature, low cellularity, and the low mitotic activity of chondrocytes, hyaline cartilage does not spontaneously regenerate. Microfracture (MF) surgery can be used to treat OA and works by stimulating production of de novo cartilage in the treated areas. However, fibrocartilage rather than hyaline cartilage forms in the area following surgery. We have recently established a human xenograft MF model in mice, enabling us to analyze the response to surgery at the cellular and molecular level, and to explore how to promote formation of hyaline, as opposed to fibrocartilage, using transplanted cells and growth factors. In our recent work we have identified three human chondroprogenitor (CP) populations by fluorescent activated cell sorting. Our project now focuses on functionally characterizing these CPs using in vitroin vivo, and transcriptomic approaches to identify if these populations give rise to unique types of cartilage. Understanding the CPs’ biases to differentiate into hyaline cartilage, and their transcriptomic identity, can help identify cellular and molecular targets that can be used to augment MF surgery.