Aims: We screened 100 diverse human embryonic stem-derived progenitor cell lines to identify novel lines with chondrogenic potential. Materials & methods: The 4D20.8 cell line was compared with mesenchymal stem cells and dental pulp stem cells by assessing osteochondral markers using immunohistochemical methods, gene expression microarrays, quantitative real-time PCR and in vivo repair of rat articular condyles. Results: 4D20.8 expressed the site-specific gene markers LHX8 and BARX1 and robustly upregulated chondrocyte markers upon differentiation. Differentiated 4D20.8 cells expressed relatively low levels of COL10A1 and lacked IHH and CD74 expression. Transplantation of 4D20.8 cells into experimentally induced defects in the femoral condyle of athymic rats resulted in cartilage and bone differentiation approximating that of the original tissue architecture. Relatively high COL2A1 and minimal COL10A1 expression occurred during differentiation in HyStem-C hydrogel with TGF-β3 and GDF-5. Conclusion: Human embryonic stem cell-derived embryonic progenitor cell lines may provide a novel means of generating purified site-specific osteochondral progenitor cell lines that are useful in research and therapy.

Original submitted 6 March 2012; Revised submitted 5 April 2012; Published online 23 April 2012

Keywords:

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 7, No. 4

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Acknowledgements

The authors would like to thank A Becker and K Beckman (Biomedical Genomics Center, University of Minnesota, MN, USA) for assistance in performing the Illumina microarray analysis. We thank E Chlipala and R Benik at Premier Laboratory (Boulder, CO, USA) for the histology work. We thank M Ghosh at Aragen Bioscience (Morgan Hill, CA, USA) for the in vivo work.

Financial & competing interests disclosure

This study was funded by BioTime, Inc. and OrthoCyte Corp. (Alameda, CA, USA), together with support from the California Institute for Regenerative Medicine. H Sternberg, KB Chapman, JT Murai, IE Erickson, WD Funk and MD West are employees of BioTime, Inc. and OrthoCyte Corp. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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