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Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering

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Abstract

The cartilage of joints, such as meniscus and articular cartilage, is normally long lasting (i.e., permanent). However, once damaged, especially in large animals and humans, joint cartilage is not spontaneously repaired. Compensating the lack of repair activity by supplying cartilage-(re)forming cells, such as chondrocytes or mesenchymal stromal cells, or by transplanting a piece of normal cartilage, has been the basis of therapy for biological restoration of damaged joint cartilage. Unfortunately, current biological therapies face problems on a number of fronts. The joint cartilage is generated de novo from a specialized cell type, termed a ‘joint progenitor’ or ‘interzone cell’ during embryogenesis. Therefore, embryonic chondroprogenitors that mimic the property of joint progenitors might be the best type of cell for regenerating joint cartilage in the adult. Pluripotent stem cells (PSCs) are expected to differentiate in culture into any somatic cell type through processes that mimic embryogenesis, making human (h)PSCs a promising source of embryonic chondroprogenitors. The major research goals toward the clinical application of PSCs in joint cartilage regeneration are to (1) efficiently generate lineage-specific chondroprogenitors from hPSCs, (2) expand the chondroprogenitors to the number needed for therapy without loss of their chondrogenic activity, and (3) direct the in vivo or in vitro differentiation of the chondroprogenitors to articular or meniscal (i.e., permanent) chondrocytes rather than growth plate (i.e., transient) chondrocytes. This review is aimed at providing the current state of research toward meeting these goals. We also include our recent achievement of successful generation of “permanent-like” cartilage from long-term expandable, hPSC-derived ectomesenchymal chondroprogenitors.

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Author notes

  1. John Y. Lee

    Present address: Miller School of Medicine, University of Miami, Miami, FL, USA

  2. Katsutsugu Umeda

    Present address: Department of Pediatrics, Kyoto University School of Medicine, Kyoto, Japan

  3. Bryan K. Ang

    Present address: Weil Cornell Medicine, New York, NY, USA

  4. Johnny Huard

    Present address: Steadman Philippon Research Institute, Vail, CO, USA

Authors and Affiliations

  1. Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston Medical School, 1825 Pressler St., Houston, TX, 77030, USA

    Naoki Nakayama, Azim Pothiawala, John Y. Lee, Nadine Matthias, Katsutsugu Umeda & Bryan K. Ang

  2. Department of Orthopaedic Surgery, The University of Texas Health Science Center at Houston Medical School, Houston, TX, USA

    Naoki Nakayama & Johnny Huard

  3. Institute of Bioscience and Technology, Texas A&M University, Houston, TX, USA

    Yun Huang & Deqiang Sun

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  1. Naoki Nakayama
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Nakayama, N., Pothiawala, A., Lee, J.Y. et al. Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering . Cell. Mol. Life Sci. 77, 2543–2563 (2020). https://doi.org/10.1007/s00018-019-03445-2

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