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Exploiting the true joint progenitor cell for articular cartilage repair

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Articular cartilage facilitates the frictionless motion of synovial joints. However, once damaged from trauma or excessive loading in daily use, repair is very poor leading to osteoarthritis (OA), a huge medical and social burden. One reason for poor cartilage repair is a limited number of stem/progenitor cells. Many cartilage and progenitor cell types have been assessed in clinical trials for therapeutic repairs with some success, but outcomes are not satisfactory due to the nature of the cells used. We propose that the “true” progenitor cells for articular cartilage repair are cells utilized in the formation of synovial joint in embryonic development.

Gdf5 and Wnt9a are earliest markers in the formation of synovial joints, but the lineage towards articular chondrocytes is not known. We have identified such specific progenitor cells in the developing interzone, site of the future synovial joint in mouse development. Using specific genetic tools in mice to track and trace these cells, we confirmed that these cells contribute directly to the formation of articular cartilage, thus can be considered as committed articular cartilage progenitor cells. Moreover, we identified that these cells express unique gene markers, co-expressing Lgr5 and Col22a1. Although these cells can be isolate from mice to repair cartilage defects, moving forward to identify similar cells in human is a hurdle due to limited accessibility to human tissues, in particular embryonic tissues. Further, it would be difficult to identify similar committed progenitor cells without the genetic tools that are available for the mouse.

Our overall goal is to exploit the cartilage regenerative capacity of human embryonic joint progenitor cells. To achieve this, we will generate mouse/human chimeras to isolate Lgr5/Col22a1 expressing human joint progenitor cells; similar to those we have identified in mouse development, and expand them in vitro. We will introduce innovative technologies using newly developed human expanded potential stem cells (EPSCs) for gene editing and generation of chimeras, and a “cloaking” system making these progenitors cells invisible to the host immune system. Thus, cartilage repair potential of these novel progenitor cells can be assess in animal models without the need for immune-suppressing drugs. The successful implementation of this project will provide a thorough understanding of the molecular regulatory mechanism involved joint formation, harnessing the information for the in vitro generation and expansion of novel committed progenitor cells with enhanced therapeutic potentials as “universal” donor cells.

You can find out more here: https://www.sbms.hku.hk/staff/danny-chan

Supervisor

Graduated from the University of Melbourne, with a Bachelor of Science (degree with honours), Master of Science and PhD, Prof Chan continued research at his alma mater on heritable skeletal disorders with a focus on extracellular matrix proteins. He joined the University of Hong Kong in 1998, maintaining his research in skeletal biology using mouse as a model to address disease mechanisms in vivo, as well as human genetic studies to define genetic risk factors for common degenerative skeletal conditions such as intervertebral disc degeneration. His research contributed to the molecular understanding of many forms of the human osteochondrodysplasias. In recognition, he was presented with “The Premier’s Award for Health & Medical Research in Victoria, Australia; and more recently, he received the Croucher Senior Fellowship from the Croucher Foundation as recognition of his contribution to skeletal research in Hong Kong.

You can find out more here: http://hub.hku.hk/cris/rp/rp00540

You can also see more details about the Faculty here: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

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