Cell yield, chondrogenic potential, and regenerated cartilage type of chondrocytes derived from ear, nasoseptal, and costal cartilage

Functional suitability and phenotypic stability of ectopic transplants are crucial factors in the clinical application of mesenchymal stem cells (MSCs) for articular cartilage repair, and might require a stringent control of chondrogenic differentiation. This study evaluated whether human bone marrow-derived MSCs adopt natural differentiation stages during induction of chondrogenesis in vitro, and whether they can form ectopic stable cartilage that is resistant to vascular invasion and calcification in vivo. During in vitro chondrogenesis of MSCs, the expression of 44 cartilage-, stem cell-, and bone-related genes and the deposition of aggrecan and types II and X collagen were determined. Similarly treated, expanded articular chondrocytes served as controls. MSC pellets were allowed to differentiate in chondrogenic medium for 3-7 weeks, after which the chondrocytes were implanted subcutaneously into SCID mice; after 4 weeks in vivo, samples were evaluated by histology. The 3-stage chondrogenic differentiation cascade initiated in MSCs was primarily characterized by sequential up-regulation of common cartilage genes. Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. In contrast, hypertrophy-associated genes were not induced in chondrocyte controls. Whereas control chondrocyte pellets resisted calcification and vascular invasion in vivo, most MSC pellets mineralized, in spite of persisting proteoglycan and type II collagen content. An unnatural pathway of differentiation to chondrocyte-like cells was induced in MSCs by common in vitro protocols. MSC pellets transplanted to ectopic sites in SCID mice underwent alterations related to endochondral ossification rather than adopting a stable chondrogenic phenotype. Further studies are needed to evaluate whether a more stringent control of MSC differentiation to chondrocytes can be achieved during cartilage repair in a natural joint environment.

Focal chondral or osteochondral defects can be painful and disabling, have a poor capacity for repair, and may predispose patients for osteoarthritis. New surgical procedures that aim to reestablish hyaline cartilage have been introduced and the results seem promising. The purpose of this study is to provide reliable data on chondral and osteochondral defects in patients with symptomatic knees requiring arthroscopy and to calculate the prevalence of patients who might benefit from cartilage repair surgery. Prospective study. One thousand consecutive knee arthroscopies were included in this study. Immediately after each arthroscopy, the surgeon completed a questionnaire providing detailed information about the findings. Chondral and osteochondral lesions were classified in accordance with the system recommended by the International Cartilage Repair Society (ICRS). Chondral or osteochondral lesions (of any type) were found in 61% of the patients. Focal chondral or osteochondral defects were found in 19% of the patients. In these patients, 61% related their current knee problem to a previous trauma, and a concomitant meniscal or anterior cruciate ligament injury was found in 42% (n = 81) and 26% (n = 50), respectively. The mean chondral or osteochondral total defect area was 2.1 cm(2) (range, 0.5 to 12; standard deviation [SD], 1.5). The main focal chondral or osteochondral defect was found on the medial femoral condyle in 58%, patella in 11%, lateral tibia in 11%, lateral femoral condyle in 9%, trochlea in 6%, and medial tibia in 5%. It has been suggested that cartilage repair surgery may be most suitable in patients younger than 40 to 50 years old. A single, well-defined ICRS grade III or IV defect with an area of at least 1 cm(2) in a patient younger than 40, 45, or 50 years accounted for 5.3%, 6.1%, and 7.1% of all arthroscopies, respectively. Our study supports the contention that articular cartilage defects are common. It has the advantages of a prospective design and use of a new classification system recommended by the ICRS. This modern system focuses on objectively measurable parameters of the lesion's extent and not its surface appearance.