Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.
<h4>Background</h4>Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-10-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976230/pdf/?tool=EBI |
| _version_ | 1818425554417745920 |
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| author | Rebecca Williams Ilyas M Khan Kirsty Richardson Larissa Nelson Helen E McCarthy Talal Analbelsi Sim K Singhrao Gary P Dowthwaite Rhiannon E Jones Duncan M Baird Holly Lewis Selwyn Roberts Hannah M Shaw Jayesh Dudhia John Fairclough Timothy Briggs Charles W Archer |
| author_facet | Rebecca Williams Ilyas M Khan Kirsty Richardson Larissa Nelson Helen E McCarthy Talal Analbelsi Sim K Singhrao Gary P Dowthwaite Rhiannon E Jones Duncan M Baird Holly Lewis Selwyn Roberts Hannah M Shaw Jayesh Dudhia John Fairclough Timothy Briggs Charles W Archer |
| author_sort | Rebecca Williams |
| collection | DOAJ |
| description | <h4>Background</h4>Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC), are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage.<h4>Methods and findings</h4>Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect.<h4>Conclusions</h4>In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell-based cartilage repair therapies due to its ability to maintain chondrogenicity upon extensive expansion unlike full-depth chondrocytes that lose this ability at only seven population doublings. |
| first_indexed | 2024-12-14T14:15:47Z |
| format | Article |
| id | doaj.art-5d9c1dff7d2e4706b3841b4a41b1b7c7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T14:15:47Z |
| publishDate | 2010-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5d9c1dff7d2e4706b3841b4a41b1b7c72022-12-21T22:58:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1324610.1371/journal.pone.0013246Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.Rebecca WilliamsIlyas M KhanKirsty RichardsonLarissa NelsonHelen E McCarthyTalal AnalbelsiSim K SinghraoGary P DowthwaiteRhiannon E JonesDuncan M BairdHolly LewisSelwyn RobertsHannah M ShawJayesh DudhiaJohn FaircloughTimothy BriggsCharles W Archer<h4>Background</h4>Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC), are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage.<h4>Methods and findings</h4>Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect.<h4>Conclusions</h4>In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell-based cartilage repair therapies due to its ability to maintain chondrogenicity upon extensive expansion unlike full-depth chondrocytes that lose this ability at only seven population doublings.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976230/pdf/?tool=EBI |
| spellingShingle | Rebecca Williams Ilyas M Khan Kirsty Richardson Larissa Nelson Helen E McCarthy Talal Analbelsi Sim K Singhrao Gary P Dowthwaite Rhiannon E Jones Duncan M Baird Holly Lewis Selwyn Roberts Hannah M Shaw Jayesh Dudhia John Fairclough Timothy Briggs Charles W Archer Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS ONE |
| title | Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. |
| title_full | Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. |
| title_fullStr | Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. |
| title_full_unstemmed | Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. |
| title_short | Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. |
| title_sort | identification and clonal characterisation of a progenitor cell sub population in normal human articular cartilage |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20976230/pdf/?tool=EBI |
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