In vitro osteogenic differentiation of human ES cells.

Since their isolation in 1998, human embryonic stem (hES) cells have been shown to be capable of adopting various cell fates in vitro. Here, we present in vitro data demonstrating the directed commitment of human embryonic stem cells to the osteogenic lineage. Human ES cells are shown to respond to factors that promote osteogenesis, leading to activation of the osteogenic markers osteocalcin, parathyroid hormone receptor, bone sialoprotein, osteopontin, cbfa1, and collagen 1. Moreover, the mineralized nodules obtained are composed of hydroxyapatite, further establishing the similarity of osteoblasts in culture to bone. These results show that osteoblasts can be derived from human ES cultures in vitro and provide the basis for comparison of adult and embryonic-derived osteogenesis, and for an investigation of potential applications for hES cells in orthopaedic tissue repair.

[1]  M. Rao,et al.  Enrichment of Neurons and Neural Precursors from Human Embryonic Stem Cells , 2001, Experimental Neurology.

[2]  Tomoki Aoyama,et al.  Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells. , 2002, Biochemical and biophysical research communications.

[3]  Makoto Sato,et al.  Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation owing to Maturational Arrest of Osteoblasts , 1997, Cell.

[4]  A. Trounson,et al.  Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro , 2000, Nature Biotechnology.

[5]  Chunhui Xu,et al.  Feeder-free growth of undifferentiated human embryonic stem cells , 2001, Nature Biotechnology.

[6]  G. Karsenty Bone formation and factors affecting this process. , 2000, Matrix biology : journal of the International Society for Matrix Biology.

[7]  Marius Wernig,et al.  In vitro differentiation of transplantable neural precursors from human embryonic stem cells , 2001, Nature Biotechnology.

[8]  D. Kaufman,et al.  Multilineage Differentiation from Human Embryonic Stem Cell Lines , 2001, Stem cells.

[9]  C. Dani,et al.  Compactin enhances osteogenesis in murine embryonic stem cells. , 2001, Biochemical and biophysical research communications.

[10]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[11]  James A. Thomson,et al.  Homologous recombination in human embryonic stem cells , 2003, Nature Biotechnology.

[12]  A. Friedenstein,et al.  Stromal stem cells: marrow-derived osteogenic precursors. , 1988, Ciba Foundation symposium.

[13]  R. Tuan,et al.  Multilineage mesenchymal differentiation potential of human trabecular bone‐derived cells , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[14]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[15]  Cun-Yu Wang,et al.  Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression , 2002, Nature Biotechnology.

[16]  R Cancedda,et al.  Repair of large bone defects with the use of autologous bone marrow stromal cells. , 2001, The New England journal of medicine.

[17]  R Cancedda,et al.  Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. , 2000, Journal of cell science.

[18]  J M Polak,et al.  Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. , 2001, Tissue engineering.

[19]  James A. Thomson,et al.  Hematopoietic colony-forming cells derived from human embryonic stem cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Itskovitz‐Eldor,et al.  Insulin production by human embryonic stem cells. , 2001, Diabetes.

[21]  Chuan Yi Tang,et al.  A 2.|E|-Bit Distributed Algorithm for the Directed Euler Trail Problem , 1993, Inf. Process. Lett..

[22]  Alon Spira,et al.  High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes: A Novel In Vitro Model for the Study of Conduction , 2002, Circulation research.

[23]  Chunhui Xu,et al.  Characterization and Enrichment of Cardiomyocytes Derived From Human Embryonic Stem Cells , 2002, Circulation research.

[24]  Sottile,et al.  Multi-lineage potential of human mesenchymal stem cells following clonal expansion. , 2001, Journal of musculoskeletal & neuronal interactions.

[25]  Cun-Yu Wang,et al.  Telomerase Accelerates Osteogenesis of Bone Marrow Stromal Stem Cells by Upregulation of CBFA1, Osterix, and Osteocalcin , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  D. Phinney Building a consensus regarding the nature and origin of mesenchymal stem cells , 2002, Journal of cellular biochemistry. Supplement.

[27]  Maya Schuldiner,et al.  Induced neuronal differentiation of human embryonic stem cells , 2001, Brain Research.

[28]  P. Bianco,et al.  Stem cells in tissue engineering , 2001, Nature.

[29]  K. Seuwen,et al.  Stem cell characteristics of human trabecular bone-derived cells. , 2002, Bone.

[30]  S. Bruder,et al.  Osteogenic differentiation of purified, culture‐expanded human mesenchymal stem cells in vitro , 1997, Journal of cellular biochemistry.

[31]  P. Bianco,et al.  Marrow stromal stem cells. , 2000, The Journal of clinical investigation.

[32]  E. Caterson,et al.  Application of mesenchymal stem cells in the regeneration of musculoskeletal tissues. , 2001, MedGenMed : Medscape general medicine.

[33]  J. Aubin,et al.  Osteoblast and chondroblast differentiation. , 1995, Bone.

[34]  J. Aubin,et al.  Kinetics of osteoprogenitor proliferation and osteoblast differentiation in vitro , 1999, Journal of cellular biochemistry.