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Characterisation of human bone marrow stromal cell heterogeneity for skeletal regeneration strategies using a two-stage colony assay and computational modelling

Sengers, Bram G., Dawson, Jonathan I. and Oreffo, Richard O.C. (2010) Characterisation of human bone marrow stromal cell heterogeneity for skeletal regeneration strategies using a two-stage colony assay and computational modelling Bone, 46, (2), pp. 496-503. (doi:10.1016/j.bone.2009.10.002).

Record type: Article

Abstract

Skeletal regeneration and tissue engineering strategies rely critically on the efficient expansion of progenitor cell populations whilst simultaneously preserving multipotentiality and the ability to induce differentiation towards bone and cartilage. Cell population heterogeneity has a significant impact on this process, but is currently poorly quantified, hampering the interpretation of experimental results and the design of optimised expansion protocols.

The objective of this study was to characterise individual human bone marrow stromal cell heterogeneity in terms of colony expansion potential. For this purpose, a novel two-stage CFU-F assay was developed in which cells from primary single cell-derived colonies were detached and reseeded again at clonal density as single cells to form new secondary colonies. This clearly demonstrated how secondary colony growth potential varies markedly both between and within primary colonies. Depending on the primary colony, cells either generated small secondary colonies only, or else a wide range of colony sizes. Using computational modelling it was shown how such colony heterogeneity could arise from hierarchical progenitor cell populations and what the limits of such a population structure were in explaining the experimental data. In addition the model demonstrated the significant potential impact of cell mobility on expansion potential and its implications for inducing population heterogeneity.

This combined experimental-computational approach will ascertain the impact of cell culture protocols on the expansion potential and functional composition of heterogeneous progenitor populations. Such insights are likely to be of crucial importance for the success of skeletal regeneration strategies

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More information

Submitted date: 23 July 2009
Published date: February 2010
Keywords: human bone marrow stromal cells, CFU-F, cell colony formation, progenitor cell hierarchy, mathematical modelling
Organisations: Bioengineering Sciences, Dev Origins of Health & Disease

Identifiers

Local EPrints ID: 71580
URI: http://eprints.soton.ac.uk/id/eprint/71580
ISSN: 8756-3282
PURE UUID: 64b746dc-42da-4a85-963b-3da7d619e541
ORCID for Bram G. Sengers: ORCID iD orcid.org/0000-0001-5859-6984
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 15 Dec 2009
Last modified: 18 Jul 2017 23:59

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