Engineering bone tissue from human embryonic stem cells

Darja Marolt, Iván Marcos Campos, Sarindr Bhumiratana, Ana Koren, Petros Petridis, Geping Zhang, Patrice F. Spitalnik, Warren L. Grayson, and Gordana Vunjak-Novakovic
PNAS published ahead of print May 14, 2012 https://doi.org/10.1073/pnas.1201830109

  1. Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved April 18, 2012 (received for review February 6, 2012)

Abstract

In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the implantation of engineered bone in immunodeficient mice for 8 wk resulted in the maintenance and maturation of bone matrix, without the formation of teratomas that is consistently observed when undifferentiated hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of principle that tissue-engineering protocols can be successfully applied to hESC progenitors to grow bone grafts for use in basic and translational studies.

Footnotes

  • ↵1Present address: The New York Stem Cell Foundation, New York, NY 10032.

  • ↵2To whom correspondence should be addressed. E-mail: gv2131{at}columbia.edu.

  • Author contributions: D.M., I.M.C., W.L.G., and G.V.-N. designed research; D.M., I.M.C., S.B., A.K., P.P., and G.Z. performed research; D.M., I.M.C., S.B., A.K., P.P., P.F.S., W.L.G., and G.V.-N. analyzed data; and D.M., W.L.G., and G.V.-N. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1201830109/-/DCSupplemental.

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Engineering bone from human embryonic stem cells
Darja Marolt, Iván Marcos Campos, Sarindr Bhumiratana, Ana Koren, Petros Petridis, Geping Zhang, Patrice F. Spitalnik, Warren L. Grayson, Gordana Vunjak-Novakovic
Proceedings of the National Academy of Sciences May 2012, 201201830; DOI: 10.1073/pnas.1201830109
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