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
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
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.
adipogenesis, bone, chondrogenesis, development, diaphysis, epiphysis, human foetal femur, osteogenesis, stro-1
1-17
Gothard, David
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Cheung, Kelvin
4466c036-4252-4eb8-919a-a299742e0786
Kanczler, Janos M.
eb8db9ff-a038-475f-9030-48eef2b0559c
Wilson, David I.
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Oreffo, Richard O.C.
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18 December 2015
Gothard, David
7ff8059e-6541-4f0f-9cdd-4f6edf0f6338
Cheung, Kelvin
4466c036-4252-4eb8-919a-a299742e0786
Kanczler, Janos M.
eb8db9ff-a038-475f-9030-48eef2b0559c
Wilson, David I.
1500fca1-7082-4271-95f4-691f1d1252a2
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Gothard, David, Cheung, Kelvin, Kanczler, Janos M., Wilson, David I. and Oreffo, Richard O.C.
(2015)
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.
Stem Cell Research & Therapy, 6 (251), .
(doi:10.1186/s13287-015-0247-2).
(PMID:26684339)
Abstract
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.
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s13287-015-0247-2.pdf
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Accepted/In Press date: 25 November 2015
Published date: 18 December 2015
Keywords:
adipogenesis, bone, chondrogenesis, development, diaphysis, epiphysis, human foetal femur, osteogenesis, stro-1
Organisations:
Human Development & Health
Identifiers
Local EPrints ID: 385270
URI: http://eprints.soton.ac.uk/id/eprint/385270
ISSN: 1757-6512
PURE UUID: 6a3c7e5a-39a2-4eba-a237-948c29e0a93f
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Date deposited: 18 Jan 2016 14:13
Last modified: 15 Mar 2024 03:23
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Author:
David Gothard
Author:
Kelvin Cheung
Author:
Janos M. Kanczler
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