Controlled differentiation of stem cells.

The extracellular microenvironment plays a significant role in controlling cellular behavior. Identification of appropriate biomaterials that support cellular attachment, proliferation and, most importantly in the case of human embryonic stem cells, lineage-specific differentiation is critical for tissue engineering and cellular therapy. In addition to growth factors and morphogenetic factors known to induce lineage commitment of stem cells, a number of scaffolding materials, including synthetic and naturally-derived biomaterials, have been utilized in tissue engineering approaches to direct differentiation. This review focuses on recent emerging findings and well-characterized differentiation models of human embryonic stem cells. Additionally, we also discuss about various strategies that have been used in stem cell expansion.

[1]  J. Hescheler,et al.  The embryoid body as a novel in vitro assay system for antiangiogenic agents. , 1998, Laboratory investigation; a journal of technical methods and pathology.

[2]  F. Barry,et al.  Gelatin-based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy. , 2000, Journal of biomedical materials research.

[3]  Peter G. Schultz,et al.  Synthetic small molecules that control stem cell fate , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Mooney,et al.  Combined Angiogenic and Osteogenic Factor Delivery Enhances Bone Marrow Stromal Cell‐Driven Bone Regeneration , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  M. Schuldiner,et al.  Differentiation of Human Embryonic Stem Cells into Embryoid Bodies Comprising the Three Embryonic Germ Layers , 1999 .

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

[7]  Young Jin Kim,et al.  Isolation of Mesenchymal Stem Cells from Cryopreserved Human Umbilical Cord Blood , 2005, International journal of hematology.

[8]  S. Matsuoka,et al.  Flk1(+) cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model. , 2007, Cardiovascular research.

[9]  J. Elisseeff,et al.  Advances in skeletal tissue engineering with hydrogels. , 2005, Orthodontics & craniofacial research.

[10]  P. Zandstra,et al.  Scalable production of embryonic stem cell-derived cells. , 2005, Methods in molecular biology.

[11]  C. Streuli,et al.  Extracellular matrix remodelling and cellular differentiation. , 1999, Current opinion in cell biology.

[12]  J. Elisseeff,et al.  Musculoskeletal Differentiation of Cells Derived from Human Embryonic Germ Cells , 2005, Stem cells.

[13]  K. Guan,et al.  Differentiation plasticity of chondrocytes derived from mouse embryonic stem cells , 2002, Journal of Cell Science.

[14]  G. Weitzer Embryonic stem cell-derived embryoid bodies: an in vitro model of eutherian pregastrulation development and early gastrulation. , 2006, Handbook of experimental pharmacology.

[15]  Jennifer H Elisseeff,et al.  Collagen mimetic peptide-conjugated photopolymerizable PEG hydrogel. , 2006, Biomaterials.

[16]  Joel Voldman,et al.  Cell patterning chip for controlling the stem cell microenvironment. , 2007, Biomaterials.

[17]  Yu Chen,et al.  Generation of functional hemangioblasts from human embryonic stem cells , 2007, Nature Methods.

[18]  D. Boettiger,et al.  Modulation of cell proliferation and differentiation through substrate-dependent changes in fibronectin conformation. , 1999, Molecular biology of the cell.

[19]  H. Kleinman,et al.  Complex Extracellular Matrices Promote Tissue‐Specific Stem Cell Differentiation , 2005, Stem cells.

[20]  Kevin Eggan,et al.  Nuclear Reprogramming of Somatic Cells After Fusion with Human Embryonic Stem Cells , 2005, Science.

[21]  Brian P Helmke,et al.  Mechanisms of mechanotransduction. , 2006, Developmental cell.

[22]  Juan J de Pablo,et al.  Inhibition of human embryonic stem cell differentiation by mechanical strain , 2006, Journal of cellular physiology.

[23]  K. Anseth,et al.  The effects of cell-matrix interactions on encapsulated beta-cell function within hydrogels functionalized with matrix-derived adhesive peptides. , 2007, Biomaterials.

[24]  S. Nishikawa,et al.  Neuroepithelial Cells Supply an Initial Transient Wave of MSC Differentiation , 2007, Cell.

[25]  J. Itskovitz‐Eldor,et al.  Differentiation of human embryonic stem cells on three-dimensional polymer scaffolds , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Kochhar,et al.  Retinoid-induced limb malformations. , 2004, Current pharmaceutical design.

[27]  M. Wiles,et al.  Hematopoietic commitment during embryonic stem cell differentiation in culture. , 1993, Molecular and cellular biology.

[28]  M. Gassmann,et al.  Differentiating embryonic stem cells into embryoid bodies. , 2004, Methods in molecular biology.

[29]  Jennifer H. Elisseeff,et al.  Engineering Structurally Organized Cartilage and Bone Tissues , 2004, Annals of Biomedical Engineering.

[30]  Xiaojun Zhao,et al.  Molecular designer self-assembling peptides. , 2006, Chemical Society reviews.

[31]  J. Itskovitz‐Eldor,et al.  Human Feeder Layers for Human Embryonic Stem Cells1 , 2003, Biology of reproduction.

[32]  M. Goldring,et al.  The control of chondrogenesis , 2006, Journal of cellular biochemistry.

[33]  Mitchell D. Probasco,et al.  Feeder-independent culture of human embryonic stem cells , 2006, Nature Methods.

[34]  W. Sufan,et al.  Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo. , 2000, Journal of biomedical materials research.

[35]  J. Itskovitz‐Eldor,et al.  Three‐dimensional porous alginate scaffolds provide a conducive environment for generation of well‐vascularized embryoid bodies from human embryonic stem cells , 2004, Biotechnology and bioengineering.

[36]  T. Nakahata,et al.  Novel Method for Efficient Production of Multipotential Hematopoietic Progenitors from Human Embryonic Stem Cells , 2007, International journal of hematology.

[37]  Shyni Varghese,et al.  Enhanced chondrogenic differentiation of murine embryonic stem cells in hydrogels with glucosamine. , 2006, Biomaterials.

[38]  Jason A Burdick,et al.  Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. , 2002, Biomaterials.

[39]  Kenneth M. Yamada,et al.  Cell interactions with three-dimensional matrices. , 2002, Current opinion in cell biology.

[40]  T. Einhorn,et al.  Osteogenic Differentiation is Selectively Promoted by Morphogenetic Signals from Chondrocytes and Synergized by a Nutrient Rich Growth Environment , 2003, Connective tissue research.

[41]  K. Lyons,et al.  BMP signaling in the cartilage growth plate. , 2006, Current topics in developmental biology.

[42]  Sangeeta N Bhatia,et al.  Microfabricated platform for studying stem cell fates , 2004, Biotechnology and bioengineering.

[43]  M L Yarmush,et al.  Sodium butyrate‐treated embryonic stem cells yield hepatocyte‐like cells expressing a glycolytic phenotype , 2006, Biotechnology and bioengineering.

[44]  J. Elisseeff,et al.  Morphogenetic signals from chondrocytes promote chondrogenic and osteogenic differentiation of mesenchymal stem cells , 2007, Journal of cellular physiology.

[45]  C. Batich,et al.  Self-assembled copper-capillary alginate gel scaffolds with oligochitosan support embryonic stem cell growth. , 2006, Journal of biomedical materials research. Part A.

[46]  Sean P. Palecek,et al.  3-D microwell culture of human embryonic stem cells. , 2006, Biomaterials.

[47]  T. Park,et al.  Integration of Cell Culture and Microfabrication Technology , 2003, Biotechnology progress.

[48]  Farshid Guilak,et al.  Adipose-derived adult stem cells for cartilage tissue engineering. , 2004, Biorheology.

[49]  Björn Rozell,et al.  A culture system using human foreskin fibroblasts as feeder cells allows production of human embryonic stem cells. , 2003, Human reproduction.

[50]  Hui Zhao,et al.  Elucidating the Secretion Proteome of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells*S , 2007, Molecular & Cellular Proteomics.

[51]  J. Elisseeff,et al.  Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. , 2000, Journal of biomedical materials research.

[52]  H. Kurosawa Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells. , 2007, Journal of bioscience and bioengineering.

[53]  D. Mooney,et al.  Bioinspired growth of crystalline carbonate apatite on biodegradable polymer substrata. , 2002, Journal of the American Chemical Society.

[54]  Jeffrey A. Hubbell,et al.  Biomaterials in Tissue Engineering , 1995, Bio/Technology.

[55]  G. Daley,et al.  Embryonic stem cell-derived hematopoietic stem cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[56]  E. Schacht,et al.  Gelatin-based microcarriers as embryonic stem cell delivery system in bone tissue engineering: an in-vitro study. , 2007, Biomacromolecules.

[57]  R. Tuan,et al.  Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation , 2007, Arthritis research & therapy.

[58]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[59]  Krista L. Niece,et al.  Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers , 2004, Science.

[60]  Robert Langer,et al.  Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells , 2007, Proceedings of the National Academy of Sciences.

[61]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[62]  R. Tuan,et al.  Transforming growth factor-beta1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation. , 2007, Experimental cell research.

[63]  Michelle Bradbury,et al.  Derivation of engraftable skeletal myoblasts from human embryonic stem cells , 2007, Nature Medicine.

[64]  A. Friedenstein,et al.  Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers , 1987, Cell and tissue kinetics.

[65]  Ana D. Lopez,et al.  Activin A Maintains Pluripotency of Human Embryonic Stem Cells in the Absence of Feeder Layers , 2005, Stem cells.

[66]  M. Itoman,et al.  Thyroid hormone-induced chondrocyte terminal differentiation in rat femur organ culture , 1998, Cell and Tissue Research.

[67]  P. Manson,et al.  The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells. , 2005, Biomaterials.

[68]  Sheng Ding,et al.  Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[69]  S. Elder Conditioned medium of mechanically compressed chick limb bud cells promotes chondrocyte differentiation , 2002, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[70]  M. Gassmann,et al.  Embryoid Bodies: An In Vitro Model of Mouse Embryogenesis , 2000, Experimental physiology.

[71]  Thomas A Einhorn,et al.  Chondrocytes Provide Morphogenic Signals That Selectively Induce Osteogenic Differentiation of Mesenchymal Stem Cells , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[72]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[73]  Lisheng Wang,et al.  Human embryonic stem cells: A journey beyond cell replacement therapies. , 2006, Cytotherapy.

[74]  S. Kawai,et al.  Chondrogenic differentiation of murine embryonic stem cells: Effects of culture conditions and dexamethasone , 2004, Journal of cellular biochemistry.

[75]  David J Mooney,et al.  VEGF Scaffolds Enhance Angiogenesis and Bone Regeneration in Irradiated Osseous Defects , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[76]  R. Cancedda,et al.  Developmental control of chondrogenesis and osteogenesis. , 2000, The International journal of developmental biology.

[77]  A. Lumsden,et al.  Cyclic strain induces vascular smooth muscle cell differentiation from murine embryonic mesenchymal progenitor cells. , 2007, Surgery.

[78]  Ralph Müller,et al.  Repair of bone defects using synthetic mimetics of collagenous extracellular matrices , 2003, Nature Biotechnology.

[79]  H. Kleinman,et al.  Cell‐Cell and Cell‐Extracellular Matrix Interactions Regulate Embryonic Stem Cell Differentiation , 2007, Stem cells.

[80]  D. Kaufman,et al.  Improved development of human embryonic stem cell‐derived embryoid bodies by stirred vessel cultivation , 2006, Biotechnology and bioengineering.

[81]  K. Leong,et al.  Significance of synthetic nanostructures in dictating cellular response. , 2005, Nanomedicine : nanotechnology, biology, and medicine.

[82]  H. Schöler,et al.  Self-renewal of embryonic stem cells by a small molecule , 2006, Proceedings of the National Academy of Sciences.

[83]  M. Salto‐Tellez,et al.  Derivation of Clinically Compliant MSCs from CD105+, CD24− Differentiated Human ESCs , 2007, Stem cells.

[84]  Richard O. Hynes,et al.  Integrin-mediated Signals Regulated by Members of the Rho Family of GTPases , 1998, The Journal of cell biology.

[85]  Daniel G. Anderson,et al.  Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells , 2004, Nature Biotechnology.

[86]  Krista L. Niece,et al.  Self-assembly combining two bioactive peptide-amphiphile molecules into nanofibers by electrostatic attraction. , 2003, Journal of the American Chemical Society.

[87]  Bernadette Ateghang,et al.  Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain‐induced cardiovascular differentiation , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[88]  Ijaz Ahmed,et al.  Three‐Dimensional Nanofibrillar Surfaces Promote Self‐Renewal in Mouse Embryonic Stem Cells , 2006, Stem cells.

[89]  B. Lahn,et al.  Neural differentiation of embryonic stem cells induced by conditioned medium from neural stem cell , 2006, Neuroreport.

[90]  Christopher S. Chen,et al.  Strategies for Engineering the Adhesive Microenvironment , 2004, Journal of Mammary Gland Biology and Neoplasia.

[91]  J. Nichols,et al.  BMP Induction of Id Proteins Suppresses Differentiation and Sustains Embryonic Stem Cell Self-Renewal in Collaboration with STAT3 , 2003, Cell.

[92]  Martin Yarmush,et al.  Alginate‐PLL microencapsulation: Effect on the differentiation of embryonic stem cells into hepatocytes , 2006, Biotechnology and bioengineering.

[93]  D. Melton,et al.  Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[94]  H. Kurosawa,et al.  A simple method for forming embryoid body from mouse embryonic stem cells. , 2003, Journal of bioscience and bioengineering.

[95]  C. Semino,et al.  Osteogenic differentiation of mouse embryonic stem cells and mouse embryonic fibroblasts in a three-dimensional self-assembling peptide scaffold. , 2006, Tissue engineering.

[96]  J. Kreuger,et al.  Building blood vessels—stem cell models in vascular biology , 2007, The Journal of cell biology.

[97]  Takehisa Matsuda,et al.  Biomaterial adherent macrophage apoptosis is increased by hydrophilic and anionic substrates in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[98]  B. Kremer,et al.  Long‐Term Culture and Differentiation of Rat Embryonic Stem Cell‐Like Cells into Neuronal, Glial, Endothelial, and Hepatic Lineages , 2003, Stem cells.

[99]  S. Gerecht,et al.  Human embryonic stem cell transplantation to repair the infarcted myocardium , 2007, Heart.

[100]  Norio Nakatsuji,et al.  Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells , 2001, Current Biology.

[101]  C. Semino,et al.  Fabrication of a three-dimensional nanostructured biomaterial for tissue engineering of bone. , 2007, Biomolecular engineering.

[102]  H. Kurosawa,et al.  A Round-bottom 96-well Polystyrene Plate Coated with 2-methacryloyloxyethyl Phosphorylcholine as an Effective Tool for Embryoid Body Formation , 2005, Cytotechnology.

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

[104]  M. Molcanyi,et al.  Neural Differentiation of Embryonic Stem Cells is Induced by Signalling from Non-Neural Niche Cells , 2006, Cellular Physiology and Biochemistry.

[105]  Benjamin G. Keselowsky,et al.  Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Aldo R Boccaccini,et al.  Chondrogenic differentiation of human embryonic stem cells: the effect of the micro-environment. , 2006, Tissue engineering.

[107]  Paolo A Netti,et al.  The effect of matrix composition of 3D constructs on embryonic stem cell differentiation. , 2005, Biomaterials.

[108]  Kevin Eggan,et al.  Non–cell autonomous effect of glia on motor neurons in an embryonic stem cell–based ALS model , 2007, Nature Neuroscience.

[109]  Ali Khademhosseini,et al.  Micropatterned cell co-cultures using layer-by-layer deposition of extracellular matrix components. , 2006, Biomaterials.

[110]  Krishnendu Roy,et al.  Effect of 3D scaffold and dynamic culture condition on the global gene expression profile of mouse embryonic stem cells. , 2006, Biomaterials.

[111]  Song Li,et al.  Anisotropic mechanosensing by mesenchymal stem cells , 2006, Proceedings of the National Academy of Sciences.

[112]  Eben Alsberg,et al.  Engineering growing tissues , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[113]  P. Schultz,et al.  Small molecules and future regenerative medicine. , 2005, Current topics in medicinal chemistry.

[114]  Chun Han,et al.  Macroscopic cartilage formation with embryonic stem-cell-derived mesodermal progenitor cells , 2003, Journal of Cell Science.

[115]  K. Gross,et al.  Colonization and maintenance of murine embryonic stem cells on poly(α-hydroxy esters) , 2004 .

[116]  G. Lepperdinger,et al.  Mesenchymal stem cell aging , 2005, Experimental Gerontology.

[117]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[118]  J. Ando,et al.  Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading , 2005, Journal of Artificial Organs.

[119]  J. Hubbell,et al.  Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. , 2005, Biophysical journal.

[120]  A. Khademhosseini,et al.  Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol) microwells. , 2007, Lab on a chip.

[121]  J. A. Hubbell,et al.  Cell‐Responsive Synthetic Hydrogels , 2003 .

[122]  S. Ramakrishna,et al.  Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. , 2005, Biomaterials.

[123]  Stephanie J Bryant,et al.  Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: Engineering gel structural changes to facilitate cartilaginous tissue production , 2004, Biotechnology and bioengineering.

[124]  K. Yamada,et al.  Integrin function: molecular hierarchies of cytoskeletal and signaling molecules , 1995, The Journal of cell biology.

[125]  R. Reiter,et al.  The enhancement of in vitro survival and chondrogenesis of limb bud cells by cartilage conditioned medium. , 1975, Developmental biology.

[126]  Peter J. Donovan,et al.  Derivation of pluripotent stem cells from cultured human primordial germ cells , 1998 .

[127]  J. Elisseeff,et al.  Hydrogels for musculoskeletal tissue engineering , 2006 .

[128]  Albert Folch,et al.  Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. , 2005, Lab on a chip.

[129]  N. Rhodes,et al.  Metabolic and histological analysis of mesenchymal stem cells grown in 3-D hyaluronan-based scaffolds , 2004, Journal of materials science. Materials in medicine.

[130]  D. Prockop Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues , 1997, Science.

[131]  Yun-Hoon Choung,et al.  Isolation and characterization of postnatal stem cells from human dental tissues. , 2007, Tissue engineering.

[132]  R. Tuan,et al.  Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture. , 2006, Osteoarthritis and cartilage.

[133]  A M Wobus,et al.  Embryonic stem cells as an in vitro model for mutagenicity, cytotoxicity and embryotoxicity studies: present state and future prospects. , 2001, Toxicology in vitro : an international journal published in association with BIBRA.

[134]  Krishnendu Roy,et al.  Biomimetic three-dimensional cultures significantly increase hematopoietic differentiation efficacy of embryonic stem cells. , 2005, Tissue engineering.

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

[136]  R. Nerem,et al.  Use of embryonic stem cell-derived endothelial cells as a cell source to generate vessel structures in vitro. , 2005, Tissue engineering.

[137]  D. Mooney,et al.  Bone regeneration in a rat cranial defect with delivery of PEI-condensed plasmid DNA encoding for bone morphogenetic protein-4 (BMP-4) , 2005, Gene Therapy.

[138]  Nathaniel S. Hwang,et al.  Chondrogenic differentiation of human embryonic stem cell-derived cells in arginine-glycine-aspartate-modified hydrogels. , 2006, Tissue engineering.

[139]  G. Keller,et al.  Embryonic stem cell differentiation: emergence of a new era in biology and medicine. , 2005, Genes & development.

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

[141]  Kevin E Healy,et al.  Hydrogels as artificial matrices for human embryonic stem cell self-renewal. , 2006, Journal of biomedical materials research. Part A.

[142]  Antonios G Mikos,et al.  In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiation. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[143]  Henrik Pedersen,et al.  Control of hepatic differentiation via cellular aggregation in an alginate microenvironment , 2007, Biotechnology and bioengineering.

[144]  Yolande Asara,et al.  Butyric and Retinoic Mixed Ester of Hyaluronan , 2004, Journal of Biological Chemistry.

[145]  Somponnat Sampattavanich,et al.  Effects of Three‐Dimensional Culture and Growth Factors on the Chondrogenic Differentiation of Murine Embryonic Stem Cells , 2006, Stem cells.

[146]  S. Nishikawa,et al.  Embryonic stem-cell culture as a tool for developmental cell biology , 2007, Nature Reviews Molecular Cell Biology.

[147]  B. Fleischmann,et al.  Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis. , 1997, Cardiovascular research.

[148]  R. Tuan,et al.  Interactive cellular modulation of chondrogenic differentiation in vitro by subpopulations of chick embryonic calvarial cells. , 1995, Developmental biology.

[149]  Robert Zweigerdt,et al.  Differentiation and lineage selection of mouse embryonic stem cells in a stirred bench scale bioreactor with automated process control. , 2005, Biotechnology and bioengineering.

[150]  R Kemler,et al.  The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. , 1985, Journal of embryology and experimental morphology.

[151]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[152]  E. Bouhassira,et al.  Differentiation of Human Embryonic Stem Cells into Bipotent Mesenchymal Stem Cells , 2006, Stem cells.

[153]  J. Itskovitz‐Eldor,et al.  Feeder Layer- and Serum-Free Culture of Human Embryonic Stem Cells1 , 2004, Biology of reproduction.

[154]  S. Shalet,et al.  Dexamethasone inhibits and thyroid hormone promotes differentiation of mouse chondrogenic ATDC5 cells. , 2002, Bone.

[155]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[156]  Austin G Smith,et al.  Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. , 2005, Bone.

[157]  Linzhao Cheng,et al.  Human Adult Marrow Cells Support Prolonged Expansion of Human Embryonic Stem Cells in Culture , 2003, Stem cells.

[158]  P. Schultz,et al.  A role for chemistry in stem cell biology , 2004, Nature Biotechnology.

[159]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[160]  Y. Ito,et al.  Surface micropatterning to regulate cell functions. , 1999, Biomaterials.

[161]  Peter W Zandstra,et al.  Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems. , 2002, Biotechnology and bioengineering.

[162]  Susan X. Hsiong,et al.  Effects of a bone-like mineral film on phenotype of adult human mesenchymal stem cells in vitro. , 2005, Biomaterials.

[163]  J. Itskovitz‐Eldor,et al.  Controlled, Scalable Embryonic Stem Cell Differentiation Culture , 2004, Stem cells.

[164]  D H Kohn,et al.  Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering. , 2000, Biomaterials.

[165]  M. Schwartz,et al.  Integrins in Mechanotransduction* , 2004, Journal of Biological Chemistry.

[166]  N. Socci,et al.  Derivation of Multipotent Mesenchymal Precursors from Human Embryonic Stem Cells , 2005, PLoS medicine.

[167]  R. Jaenisch,et al.  In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state , 2007, Nature.

[168]  F. Long,et al.  Regulation of endochondral cartilage growth in the developing avian limb: cooperative involvement of perichondrium and periosteum. , 2001, Developmental biology.

[169]  Krishnendu Roy,et al.  Influence of scaffold physical properties and stromal cell coculture on hematopoietic differentiation of mouse embryonic stem cells. , 2006, Biomaterials.

[170]  J. Thomson,et al.  Derivation of human embryonic stem cells in defined conditions , 2006, Nature Biotechnology.

[171]  T. McDevitt,et al.  Rotary Suspension Culture Enhances the Efficiency, Yield, and Homogeneity of Embryoid Body Differentiation , 2007, Stem cells.

[172]  R. S. Goldstein,et al.  Peripheral sensory neurons differentiate from neural precursors derived from human embryonic stem cells. , 2008, Differentiation; research in biological diversity.

[173]  J. Schneider,et al.  Self-assembling peptides and proteins for nanotechnological applications. , 2004, Current opinion in structural biology.

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

[175]  T. Ichisaka,et al.  Generation of germline-competent induced pluripotent stem cells , 2007, Nature.

[176]  Andrew Scutt,et al.  Age‐related impairment of mesenchymal progenitor cell function , 2006, Aging cell.

[177]  N. Zini,et al.  Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold. , 2005, Biomaterials.

[178]  Akihiko Takashima,et al.  Electrical Stimulation Modulates Fate Determination of Differentiating Embryonic Stem Cells , 2007, Stem cells.

[179]  Ali Khademhosseini,et al.  Co-culture of human embryonic stem cells with murine embryonic fibroblasts on microwell-patterned substrates. , 2006, Biomaterials.

[180]  Vivian H. Fan,et al.  Tethered Epidermal Growth Factor Provides a Survival Advantage to Mesenchymal Stem Cells , 2007, Stem cells.

[181]  C. Sharp,et al.  Epigenetic reprogramming of nonreplicating somatic cells for long-term proliferation by temporary cell-cell contact. , 2007, Stem cells and development.

[182]  D. Ilic,et al.  Culture of human embryonic stem cells and the extracellular matrix microenvironment. , 2006, Regenerative medicine.

[183]  M. Richards,et al.  Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cells , 2002, Nature Biotechnology.

[184]  F. Gage,et al.  Human embryonic stem cells express an immunogenic nonhuman sialic acid , 2005, Nature Medicine.