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.
Highlights
Articular cartilage defects have been reported in up to 20% of all patients undergoing arthroscopy of the knee [1,2,3,4]
The difference between the Bone marrow (BM)-mesenchymal stem cells (MSCs) and the OA chondrocytes for mean expression of COL1A1, COL2A1, and COL10A1 at day 21 were approximately 6 fold, 3 fold and 85 fold, respectively
The expression of COL2A1 on day 7 was considerably higher in OA chondrocytes than in BM-MSC derived chondrocytes, consistent with retained expression of COL2A1 in the chondrocytes in the course of in vitro culture
Summary
Articular cartilage defects have been reported in up to 20% of all patients undergoing arthroscopy of the knee [1,2,3,4]. Lesions of hyaline articular cartilage heal poorly. Untreated defects will usually give rise to pain, functional impairment, and eventually osteoarthritis (OA) [5,6]. OA may arise as a primary degenerative lesion of the hyaline cartilage [7]. Several treatment modalities have been developed over the past decades in attempts to reestablish fully functional cartilage tissue [8]. The repair tissue generated following ACI frequently contains fibrocartilage, and ACI has not proven to be superior to other surgical techniques [10,11,12]. OA patients frequently end up having total joint replacement surgery
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