Distinct mesenchymal progenitor cell subsets in the adult human synovium

Alexandra Karystinou, Francesco Dell'Accio, Tobias B. A. Kurth, Henning Wackerhage, Ilyas M. Khan, Charles W. Archer, Elena A. Jones, Thimios A. Mitsiadis, Cosimo De Bari

Research output: Contribution to journalArticle

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Abstract

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 beta-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.
Original languageEnglish
Pages (from-to)1057-1064
Number of pages8
JournalRheumatology
Volume48
Issue number9
Early online date14 Jul 2009
DOIs
Publication statusPublished - Sep 2009

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Synovial Membrane
Mesenchymal Stromal Cells
Telomerase
Clone Cells
Population
Cell Aging
Telomere
beta-Galactosidase
Knee Joint
Southern Blotting
Flow Cytometry
Stem Cells
Tissue Donors
Staining and Labeling
Phenotype
Growth

Keywords

  • aged
  • aged, 80 and over
  • cell aging
  • cell division
  • cells, cultured
  • chondrogenesis
  • female
  • humans
  • immunophenotyping
  • knee joint
  • male
  • mesenchymal stem cells
  • middle aged
  • osteogenesis
  • synovial membrane
  • telomerase
  • telomere
  • clones
  • synovium
  • regenerative medicine

Cite this

Karystinou, A., Dell'Accio, F., Kurth, T. B. A., Wackerhage, H., Khan, I. M., Archer, C. W., ... De Bari, C. (2009). Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology, 48(9), 1057-1064. https://doi.org/10.1093/rheumatology/kep192

Distinct mesenchymal progenitor cell subsets in the adult human synovium. / Karystinou, Alexandra; Dell'Accio, Francesco; Kurth, Tobias B. A.; Wackerhage, Henning; Khan, Ilyas M.; Archer, Charles W.; Jones, Elena A.; Mitsiadis, Thimios A.; De Bari, Cosimo.

In: Rheumatology, Vol. 48, No. 9, 09.2009, p. 1057-1064.

Research output: Contribution to journalArticle

Karystinou, A, Dell'Accio, F, Kurth, TBA, Wackerhage, H, Khan, IM, Archer, CW, Jones, EA, Mitsiadis, TA & De Bari, C 2009, 'Distinct mesenchymal progenitor cell subsets in the adult human synovium', Rheumatology, vol. 48, no. 9, pp. 1057-1064. https://doi.org/10.1093/rheumatology/kep192
Karystinou A, Dell'Accio F, Kurth TBA, Wackerhage H, Khan IM, Archer CW et al. Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology. 2009 Sep;48(9):1057-1064. https://doi.org/10.1093/rheumatology/kep192
Karystinou, Alexandra ; Dell'Accio, Francesco ; Kurth, Tobias B. A. ; Wackerhage, Henning ; Khan, Ilyas M. ; Archer, Charles W. ; Jones, Elena A. ; Mitsiadis, Thimios A. ; De Bari, Cosimo. / Distinct mesenchymal progenitor cell subsets in the adult human synovium. In: Rheumatology. 2009 ; Vol. 48, No. 9. pp. 1057-1064.
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AU - Dell'Accio, Francesco

AU - Kurth, Tobias B. A.

AU - Wackerhage, Henning

AU - Khan, Ilyas M.

AU - Archer, Charles W.

AU - Jones, Elena A.

AU - Mitsiadis, Thimios A.

AU - De Bari, Cosimo

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N2 - 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 beta-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.

AB - 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 beta-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.

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KW - male

KW - mesenchymal stem cells

KW - middle aged

KW - osteogenesis

KW - synovial membrane

KW - telomerase

KW - telomere

KW - clones

KW - synovium

KW - regenerative medicine

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DO - 10.1093/rheumatology/kep192

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SP - 1057

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JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

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