The University of Southampton
University of Southampton Institutional Repository

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
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
1757-6512
1-17
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
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), 1-17. (doi:10.1186/s13287-015-0247-2). (PMID:26684339)

Record type: Article

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.

Text
s13287-015-0247-2.pdf - Version of Record
Available under License Creative Commons Attribution.
Download (4MB)

More information

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
ORCID for Janos M. Kanczler: ORCID iD orcid.org/0000-0001-7249-0414
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 18 Jan 2016 14:13
Last modified: 12 Jul 2024 01:43

Export record

Altmetrics

Contributors

Author: David Gothard
Author: Kelvin Cheung
Author: Janos M. Kanczler ORCID iD
Author: David I. Wilson

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×