Rheumatology Advance Access originally published online on July 14, 2009
Rheumatology 2009 48(9):1057-1064; doi:10.1093/rheumatology/kep192
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Distinct mesenchymal progenitor cell subsets in the adult human synovium
1Division of Applied Medicine, University of Aberdeen, Aberdeen, 2Centre for Experimental Medicine and Rheumatology, Queen Mary, University of London, London, 3Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, 4Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK and 5Institute of Oral Biology, University of Zurich, Zurich, Switzerland.
Correspondence to: Cosimo De Bari, Division of Applied Medicine, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail: c.debari{at}abdn.ac.uk
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Abstract |
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Objective. To analyse the heterogeneity at the single-cell level of human mesenchymal progenitor cells from SM.
Methods. Cell populations were enzymatically released from the knee joint synovium of adult human individuals. Single cell-derived clonal populations were obtained by limiting dilution and serially passaged to determine growth rates. Phenotypic analysis was carried out by flow cytometry. Replicative senescence was assessed by the senescence-associated β-galactosidase staining. Telomere lengths were determined semiquantitatively by Southern blotting. Telomerase activity was measured using a real-time quantitative telomerase repeat amplification procedure. Culture-expanded clonal populations were subjected to in vitro differentiation assays to investigate their mesenchymal multipotency.
Results. The 50 clones analysed displayed wide variations in the proliferation rates, even within the same donor sample. The time taken to reach 20 population doublings ranged from 44 to 130 days. The phenotype of the clones tested was compatible with that of mesenchymal stem cells. Mean telomere lengths ranged from 5.2 to 10.9 kb with positive linear trend with telomerase activity, but no correlation with proliferative rates or cell senescence. All clones tested were capable of chondrogenic and osteogenic differentiation, though with large variability in potency. In contrast, only 30% of the clones were adipogenic.
Conclusions. We report for the first time the co-existence, within the synovium, of progenitor cell subsets with distinct mesenchymal differentiation potency. Our findings further emphasize the need for strategies to purify cell populations with the clinically desired tissue formation potentials.
KEY WORDS: Mesenchymal stem cells, Synovium, Clones, Chondrogenesis, Osteogenesis, Regenerative medicine
Submitted 4 February 2009;
revised version accepted 5 June 2009.
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