Award details

Osteogenic differentiation of human embryonic stem cells in 3-D culture

Reference	BB/C505840/1
Principal Investigator / Supervisor	Dr Lee Buttery
Co-Investigators / Co-Supervisors
Institution	University of Nottingham
Department	Sch of Pharmacy
Funding type	Research
Value (£)	236,849
Status	Completed
Type	Research Grant
Start date	01/03/2005
End date	29/02/2008
Duration	36 months

Abstract

Tissue damage and defects whether developmental, traumatic or degenerative, constitute a major health problem. They are potentially treatable by stem cells, but this requires identification of cells with the capacity to give rise to functional tissue of therapeutically useful size. Embryonic stem (ES) cells offer a potential solution, as they can be grown almost indefinitely and can be coaxed into forming any cell type. While it is possible to guide ES cells differentiation by stimulating monolayer cultures with soluble factors, if we are to successfully develop ES cells for tissue repair we must also be able to control their differentiation in 3-D environments. This project will investigate growth and osteogenic differentiation of human ES cells in artificial, extracellular 3-D environments created by porous resorbable bioactive scaffolds. Polymers (e.g. poly-alpha-hydroxy acids), will be used to form scaffold templates and it is proposed that through specific modification of its architecture (e.g. porosity, pore size, surface roughness) and its chemistry (e.g. coating with biaoctive molecules) it will be possible to control ES cell differentiation and select specific cell types. Cell/scaffold constructs will be maintained in stirred bioreactors. The chick chorioallantoic membrane assay will be used to investigate differentiation ex vivo and assess for correlations between scaffold structure/chemistry, induction of osteogenesis and fibrovascular invasion. The study will use existing human ES cell lines (e.g. H1, WiCell) and focus on deriving osteoblastic cells and investigating the basic mechanisms of osteogenesis (e.g. osteochondral or intramembraneous ossification). The defined, measurable end-point of this proposal is conversion of ES cells into osteoblastic cells on vascularized 3-D scaffolds and production of more accurate homologues (compared to monolayer culture) of endogenous bone tissue.

Summary

unavailable

Committee	Closed Committee - Engineering & Biological Systems (EBS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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