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Bone from blood: Optimised isolation, characterisation and osteogenic induction of mesenchymal stem cells from umbilical cord blood

Objective

There is an urgent clinical requirement for appropriate bone substitutes that are able to replace current autologous and allogeneic grafting procedures for the repair of diseased or damaged skeletal tissues. Mesenchymal stem cells (MSCs), found predominantly in the bone marrow, are able to differentiate into osteogenic, chondrogenic, adipogenic and tenogenic lineages, thus offering considerable therapeutic potential for tissue engineering applications. However, invasive extraction procedures and insufficient viable cell yields have necessitated the identification of alternative tissue sources of MSCs. Growing evidence suggests that umbilical cord blood (UCB) contains a population of rare MSCs that are able to undergo multilineage differentiation.
The aim of this proposal is optimise the isolation and expansion of MSCs from human UCB (CB-MSCs). The differentiation capacity of CB-MSCs will be examined, with a specific focus on osteogenesis. The CB-MSCs will be characterised by genomic, proteomic and bioimpedance profiling and compared to MSCs isolated from human bone marrow as well as embryonic stem cells. Full bioinformatics integration of datasets will identify specific and/or novel signalling factors associated with CB-MSCs. The immunophenotype and alloreactivity of CB-MSCs will be determined. Comparative analyses of the population doubling times, telomere length and telomerase activity will identify the lifespan of CB-MSCs. Novel expansion techniques will be combined with scale-up procedures and the generation of CB-MSC lines for banking using optimised cryopreservation protocols. In vitro and in vivo biocompatibility assays using a range of biomimetic scaffolds will be exploited, complementing in vivo homing and engraftment models. Our integrated approach using complementary expertise will provide a timely and thorough evaluation of CB-MSCs and define appropriate routes for their therapeutic implementation.

Call for proposal

FP6-2004-LIFESCIHEALTH-5
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Coordinator

UNIVERSITY OF YORK
EU contribution
No data
Address
Heslington
YORK
United Kingdom

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Participants (9)