title: Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.
abstract: Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA) may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM) derived mesenchymal stem cells (MSCs) from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin), ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.
authors.affiliation: The Norwegian Center for Stem Cell Research, University of Oslo, Oslo, Norway.
authors.forename: Amilton M
authors.initials: AM
authors.lastname: Fernandes
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Herlofsen
authors.forename: Tommy A
authors.initials: TA
authors.lastname: Karlsen
authors.forename: Axel M
authors.initials: AM
authors.lastname: Küchler
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Fløisand
authors.forename: Jan E
authors.initials: JE
authors.lastname: Brinchmann
mesh_terms: D000368:Aged; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000464:Alginates / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020723:Glucuronic Acid / Q000737:chemistry; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D000464:Alginates; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D024043:Collagen Type II; D053823:Hedgehog Proteins; D006603:Hexuronic Acids; C509246:IHH protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D053495:Osteopontin; D020723:Glucuronic Acid