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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 24 FEB 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 2, pages 206–216, February 2011
How to Cite
Bilousova, G., Jun, D. H., King, K. B., De Langhe, S., Chick, W. S., Torchia, E. C., Chow, K. S., Klemm, D. J., Roop, D. R. and Majka, S. M. (2011), Osteoblasts Derived from Induced Pluripotent Stem Cells form Calcified Structures in Scaffolds Both In Vitro and In Vivo. STEM CELLS, 29: 206–216. doi: 10.1002/stem.566
G.B.: conception and design, collection and/or assembly of data, provision of study material or patients data analysis and interpretation, manuscript writing; D.H.J.: conception and design, collection and/or assembly of data, data analysis and interpretation; K.B.K.: provision of study material or patients, data analysis and interpretation, final approval of manuscript; S.D.L.: collection and/or assembly of data; W.S.C.: conception and design; E.C.T.: collection and/or assembly of data, data analysis and interpretation; K.S.C.: collection and/or assembly of data, data analysis and interpretation; D.J.K.: collection and/or assembly of data, data analysis and interpretation; D.R.R.: financial support, provision of study material or patients; S.M.M.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript. G.B. and D.H.J. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 23, 2010.
- Issue published online: 24 FEB 2011
- Article first published online: 24 FEB 2011
- Accepted manuscript online: 23 NOV 2010 07:30AM EST
- Manuscript Accepted: 9 NOV 2010
- Manuscript Received: 3 AUG 2010
- Unknown funding agency. Grant Numbers: R03HL096382-01, 1R01 HL091105-01
- NIH. Grant Numbers: AR052263, AR50252
- Dystrophic Epidermolysis Bullosa Research Association (DebRA) International from DebRA Austria
- DK NIDDK. Grant Number: R01-078966
- iPS cells;
- Mesenchymal lineages
Reprogramming somatic cells into an ESC-like state, or induced pluripotent stem (iPS) cells, has emerged as a promising new venue for customized cell therapies. In this study, we performed directed differentiation to assess the ability of murine iPS cells to differentiate into bone, cartilage, and fat in vitro and to maintain an osteoblast phenotype on a scaffold in vitro and in vivo. Embryoid bodies derived from murine iPS cells were cultured in differentiation medium for 8–12 weeks. Differentiation was assessed by lineage-specific morphology, gene expression, histological stain, and immunostaining to detect matrix deposition. After 12 weeks of expansion, iPS-derived osteoblasts were seeded in a gelfoam matrix followed by subcutaneous implantation in syngenic imprinting control region (ICR) mice. Implants were harvested at 12 weeks, histological analyses of cell and mineral and matrix content were performed. Differentiation of iPS cells into mesenchymal lineages of bone, cartilage, and fat was confirmed by morphology and expression of lineage-specific genes. Isolated implants of iPS cell-derived osteoblasts expressed matrices characteristic of bone, including osteocalcin and bone sialoprotein. Implants were also stained with alizarin red and von Kossa, demonstrating mineralization and persistence of an osteoblast phenotype. Recruitment of vasculature and microvascularization of the implant was also detected. Taken together, these data demonstrate functional osteoblast differentiation from iPS cells both in vitro and in vivo and reveal a source of cells, which merit evaluation for their potential uses in orthopedic medicine and understanding of molecular mechanisms of orthopedic disease. STEM CELLS 2011;29:206–216