title: Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis.
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.
authors.affiliation: Gene Expression Laboratories, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Sheng-Lian
authors.initials: SL
authors.lastname: Yang
authors.forename: Erica
authors.initials: E
authors.lastname: Harnish
authors.forename: Thomas
authors.initials: T
authors.lastname: Leeuw
authors.forename: Uwe
authors.initials: U
authors.lastname: Dietz
authors.forename: Erika
authors.initials: E
authors.lastname: Batchelder
authors.forename: Paul S
authors.initials: PS
authors.lastname: Wright
authors.forename: Jane
authors.initials: J
authors.lastname: Peppard
authors.forename: Paul
authors.initials: P
authors.lastname: August
authors.forename: Cecile
authors.initials: C
authors.lastname: Volle-Challier
authors.forename: Francoise
authors.initials: F
authors.lastname: Bono
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisua Belmonte
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D010455:Peptides; D054852:Small Molecule Libraries; D008156:Luciferases