Communication

Protein & Cell

, Volume 3, Issue 12, pp 934-942

Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis

  • Sheng-Lian YangAffiliated withGene Expression Laboratories, The Salk Institute for Biological Studies
  • , Erica HarnishAffiliated withSanofi US, R&D, Early to Candidate Unit, Tucson Research Center
  • , Thomas LeeuwAffiliated withSanofi Deutschland GmbH, R&D, TSU Aging Quality of Life, Industriepark Hoechst
  • , Uwe DietzAffiliated withSanofi Deutschland GmbH, R&D, TSU Aging Quality of Life, Industriepark Hoechst
  • , Erika BatchelderAffiliated withGene Expression Laboratories, The Salk Institute for Biological Studies
  • , Paul S. WrightAffiliated withSanofi US, R&D, Early to Candidate Unit, Tucson Research Center
  • , Jane PeppardAffiliated withSanofi US, R&D, Early to Candidate Unit, Tucson Research Center
  • , Paul AugustAffiliated withSanofi US, R&D, Early to Candidate Unit, Tucson Research Center
  • , Cecile Volle-ChallierAffiliated withSanofi R&D, Early to Candidate Unit
    • , Francoise BonoAffiliated withSanofi R&D, Early to Candidate Unit
    • , Jean-Marc HerbertAffiliated withSanofi R&D, Early to Candidate Unit
    • , Juan Carlos Izpisua BelmonteAffiliated withGene Expression Laboratories, The Salk Institute for Biological StudiesCenter of Regeneration Medicine Email author 

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Abstract

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement. Microfracture, an articular cartilage repair surgical technique, has been commonly used in the clinic to induce the repair of tissue at damage sites. Mesenchymal stem cells (MSC) have also been used as cell therapy to repair degenerated cartilage. However, the therapeutic outcomes of all these techniques vary in different patients depending on their age, health, lesion size and the extent of damage to the cartilage. The repairing tissues either form fibrocartilage or go into a hypertrophic stage, both of which do not reproduce the equivalent functionality of endogenous hyaline cartilage. One of the reasons for this is inefficient chondrogenesis by endogenous and exogenous MSC. Drugs that promote chondrogenesis could be used to induce self-repair of damaged cartilage as a non-invasive approach alone, or combined with other techniques to greatly assist the therapeutic outcomes. The recent development of human induced pluripotent stem cell (iPSCs), which are able to self-renew and differentiate into multiple cell types, provides a potentially valuable cell resource for drug screening in a “more relevant” cell type. Here we report a screening platform using human iPSCs in a multi-well plate format to identify compounds that could promote chondrogenesis.

Keywords

hESC hiPSC chondrogenesis compound screening platform