Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.
Rebecca
R
Williams
Ilyas M
IM
Khan
Kirsty
K
Richardson
Larissa
L
Nelson
Helen E
HE
McCarthy
Talal
T
Analbelsi
Sim K
SK
Singhrao
Gary P
GP
Dowthwaite
Rhiannon E
RE
Jones
Duncan M
DM
Baird
Holly
H
Lewis
Selwyn
S
Roberts
Hannah M
HM
Shaw
Jayesh
J
Dudhia
John
J
Fairclough
Timothy
T
Briggs
Charles W
CW
Archer
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002358:Cartilage, Articular / Q000166:cytology*; D002454:Cell Differentiation; D002460:Cell Line; D002648:Child; D017931:DNA Primers; D005353:Fibronectins / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere
D017931:DNA Primers; D005353:Fibronectins; D019098:Telomerase