Human embryonic stem cells mend massive skull injury

Human embryonic stem cells mend massive skull injury in mice Sunday, 02 December 2007 Broken skulls can be repaired using cells from human embryos, scientists have shown. Researchers were able to plug holes in the skulls of mice by transplanting human embryonic stem cells (hESCs), which grew into new bone tissue. Although at an early stage, the experiment indicated one way that hESCs, or cells like them, might be used in practical treatments. Healing critical-size defects (defects that would not otherwise heal on their own) in intramembraneous bone, the flat bone type that forms the skull, is a vivid demonstration of new techniques devised by researchers at John Hopkins University to use hESCs for tissue regeneration. Using mesenchymal precursor cells isolated from hESCs, the Hopkins team steered them into bone regeneration by using “scaffolds,” tiny, three-dimensional platforms made from biomaterials. Physical context, it turns out, is a powerful influence on cell fate. Nathaniel S. Hwang, Jennifer Elisseeff, and colleagues at Whitaker Biomedical Engineering Institute, Department of Biomedical Engineering, at John Hopkins demonstrated that by changing the scaffold materials, they could shift mesenchymal precursor cells into either of the body’s osteogenic pathways: intramembraneous, which makes skull, jaw, and clavicle bone; or endochondral, which builds the “long” bones and involves initial formation of cartilage, which is then transformed into bone by mineralization. Mesenchymal precursor cells grown on an all-polymer, biodegradable scaffold followed the endochondral lineage. Those grown on a composite scaffold made of biodegradable polymers and a hard, gritty mineral called hydroxyapatite went to the intramembraneous side. Biomaterial scaffolds provide a three-dimensional framework on which cells can proliferate and differentiate, secrete extracellular matrix, and form functional tissues, says Hwang. In addition, their known composition allowed the researchers to characterize the extracellular micro-environmental cues that drive the lineage specification. The promise of pluripotent embryonic stem cells for regenerative medicine hangs on the development of such control techniques. Left to themselves, hESCs in culture differentiate wildly, forming a highly mixed population of cell types, which is of little use for cell-based therapy or for studying particular lineages. Conventional hESC differentiation protocols rely on growth factors, co-culture, or genetic manipulation, say the researchers. The scaffolds offer a much more efficient method. As a proof of principle, Hwang and colleagues seeded hESC-derived mesenchymal cells onto hydroxyapatite-composite scaffolds and used the resulting intramembraneous bone cells to successfully heal large skull defects in mice. The Hopkins researchers believe that this is the first study to demonstrate a potential application of hESC-derived mesenchymal cells in a musculoskeletal tissue regeneration application. (Presented at American Society for Cell Biology's 47th Annual Meeting in Washington, D.C., Abstract B312 Biomaterials-directed In Vivo Commitment of Mesenchymal Cells Derived from Human Embryonic Stem Cells. N. S. Hwang, S. Varghese, J. Elisseeff; Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA) ......... ZenMaster

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