Rheumatology Advance Access originally published online on September 26, 2007
Rheumatology 2007 46(11):1676-1683; doi:10.1093/rheumatology/kem217
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A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis
1The Leeds Institute of Molecular Medicine, University of Leeds, University of Leeds, Leeds and 2The Calderdale Royal Hospital, Salterhebble, Halifax, West Yorkshire, UK.
Correspondence to: Prof. Dennis McGonagle, The University of Leeds, WT Brenner Building, Level 6, St James Hospital, Leeds LS9 7TF, UK. E-mail: d.g.mcgonagle{at}leeds.ac.uk
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Abstract |
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Objectives. The utility of autologous chondrocytes for cartilage repair strategies in older subjects with osteoarthritis (OA) may be limited by both age-related and disease-associated decline in chondrogenesis. The aim of this work was to assess OA Hoffa's fat pad as an alternative source of autologous chondroprogenitor cells and to compare it with OA chondrocytes derived from different areas of cartilage.
Methods. Cartilage and fat pad tissue digests were obtained from 26 subjects with knee OA and compared with normal bone marrow (BM) mesenchymal stem cells (MSCs) with respect to their in vitro colony-forming potential, growth kinetics, multipotentiality and clonogenicity. Flow cytometry was used to investigate their MSC marker phenotype.
Results. Expanded cultures derived from eroded areas of cartilage were slightly more chondrogenic than those derived from macroscopically normal cartilage or chondro-osteophytes; however, all cartilage-derived cultures failed to maintain their chondrogenic potency following extended expansion. In contrast, OA fat pads contained highly clonogenic and multipotential cells with stable chondrogenic potency in vitro, even after 16 population doublings. Standard colony-forming assays failed to reflect the observed functional differences between the studied tissues whereas flow cytometry revealed higher levels of a putative MSC marker low-affinity growth factor receptor (LNGFR) on culture expanded fat pad-derived, but not cartilage-derived, MSCs.
Conclusions. In contrast to OA cartilage from three different sites, OA Hoffa's fat pad contains clonogenic cells that meet the criteria for MSCs and produce multipotential cultures that maintain their chondrogenesis long term. These findings have broad implications for future strategies aimed at cartilage repair in OA.
KEY WORDS: Mesenchymal Stem Cells, Osteoarthritis, Cartilage
Submitted 7 February 2007;
revised version accepted 17 July 2007.
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