Synovial fluid mesenchymal stem cells in health and early osteoarthritis: detection and functional evaluation at the single-cell level.
OBJECTIVE
Arthritic synovial fluid (SF) contains mesenchymal stem cells (MSCs), which could simply reflect their shedding from diseased joint structures. This study used the bovine model to explore SF MSCs in health and enumerated them at the earliest stages of human osteoarthritis (OA) in radiographically normal joints.


METHODS
Clonogenicity and multipotentiality of normal bovine SF MSCs were compared with donor-matched bone marrow (BM) MSCs at the single-cell level. The colony-forming unit-fibroblastic assay was used for MSC enumeration. The XTT assay was employed to assess cell proliferation, and flow cytometry was used to investigate the marker phenotype of bovine and human SF MSCs.


RESULTS
Single MSCs were present in normal bovine SF, and 96% of them were able to expand at least 1 million-fold. These cells were CD271-, multipotential, considerably more clonogenic, and less adipogenic than matched BM MSCs. In both pellet assays and on polyglycolic acid scaffolds, SF clones displayed consistent chondrogenic differentiation, while BM clones were variable. MSCs were present in arthroscopically normal human joints and were increased 7-fold in early OA (P = 0.034). Their numbers correlated with numbers of free microscopic synovial tissue fragments (r = 0.826, P < 0.0001). OA SF had a growth-promoting effect on synovial MSCs.


CONCLUSIONS
This study confirms the presence of MSCs in normal SF and shows their numerical increase in early human OA. SF MSCs are likely to originate from synovium. These findings provide a platform for the exploration of the potential role of SF MSCs in joint homeostasis and for investigation of their utility in novel joint regeneration strategies.
University of Leeds, Leeds, UK. msjej@leeds.ac.uk
Elena A
EA
Jones
Aileen
A
Crawford
Anne
A
English
Karen
K
Henshaw
Jenifer
J
Mundy
Diane
D
Corscadden
Tony
T
Chapman
Paul
P
Emery
Paul
P
Hatton
Dennis
D
McGonagle
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000473:pathology* / Q000503:physiopathology; D013582:Synovial Fluid / Q000166:cytology*; D054457:Tissue Scaffolds