Expression of Brachyury in mesenchymal progenitor cells leads to cartilage-like tissue that is resistant to the destructive effect of rheumatoid arthritis synovial fibroblasts.
Our objectives were to determine the chondrogenic potential of a murine Brachyury-transformed mesenchymal progenitor cell line in the presence of rheumatoid arthritis-activated synovial fibroblasts (RASFs). Brachyury-transformed mesenchymal progenitor cells were implanted alone or combined with RASFs isolated from diseased human joints in each of six immunodeficient SCID mice. De novo tissue formation was analysed by histology and immunohistochemistry after 60 days. Spheroid nodules resembling cartilage morphologically and by the expression of proteoglycans and collagen II developed in four of six implants in the absence and in five of six implants in the presence of RASFs. No evidence for hypertrophic differentiation could be observed. Mesenchymal progenitor cells transformed with Brachyury are able to produce a cartilage like tissue in vivo over an extended period of time that is resistant to the destructive effect of RASF. This observation may provide opportunities for a cell-based reconstructive treatment in joint disease.
Dinser
Robert
R
Department of Internal Medicine and Rheumatology, Justus-Liebig Universität Giessen, Kerckhoff-Hospital, Bad Nauheim, Germany. r.dinser@kerckhoff-klinik.de
Pelled
Gadi
G
Müller-Ladner
Ulf
U
Gazit
Dan
D
Neumann
Elena
E
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002356:Cartilage / Q000166:cytology*; D005260:Female; D005326:Fetal Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000473:pathology; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D013583:Synovial Membrane / Q000473:pathology*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098908:Brachyury Protein
D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein