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Background  Adult skeletal stem cells (SSCs) often exhibit limited  in vitro  expansion with undesirable phenotypic changes and loss of differentiation capacity. Foetal tissues offer an alternative cell source, providing SSCs which exhibit desirable differentiation capacity over prolonged periods, ideal for extensive  in vitro  and  ex vivo  investigation of fundamental bone biology and skeletal development.    Methods  We have examined the derivation of distinct cell populations from human foetal femora. Regionally isolated populations including epiphyseal and diaphyseal cells were carefully dissected. Expression of the SSC marker Stro-1 was also found in human foetal femora over a range of developmental stages and subsequently utilised for immuno-selection.    Results  Regional populations exhibited chondrogenic (epiphyseal) and osteogenic (diaphyseal) phenotypes following  in vitro  and  ex vivo  characterisation and molecular analysis, indicative of native SSC maturation during skeletal development. However, each population exhibited potential for induced multi-lineage differentiation towards bone (bone nodule formation), cartilage (proteoglycan and mucopolysaccharide deposition) and fat (lipid deposition), suggesting the presence of a shared stem cell sub-population. This shared sub-population may be comprised of Stro-1+ cells, which were later identified and immuno-selected from whole foetal femora exhibiting multi-lineage differentiation capacity  in vitro  and  ex vivo .    Conclusions  Distinct populations were isolated from human foetal femora expressing osteochondral differentiation capacity. Stro-1 immuno-selected SSCs were isolated from whole femora expressing desirable multi-lineage differentiation capacity over prolonged  in vitro  expansion, superior to their adult-derived counterparts, providing a valuable cell source with which to study bone biology and skeletal development.    Electronic supplementary material  The online version of this article (doi:10.1186/s13287-015-0247-2) contains supplementary material, which is available to authorized users.

stem cell research and therapy

Regionally-derived cell populations and skeletal stem cells from human foetal femora exhibit specific osteochondral and multi-lineage differentiation capacity in vitro and ex vivo