Matrix-Associated Implantation of Predifferentiated Mesenchymal Stem Cells Versus Articular Chondrocytes

Abstract

Background: The use of predifferentiated mesenchymal stem cells (MSC) leads to better histological results compared with undifferentiated MSC in sheep. This raises the need for a longer term follow-up study and comparison with a clinically established method. Hypothesis: We hypothesized that chondrogenic in vitro predifferentiation of autologous MSC embedded in a collagen I hydrogel leads to better structural repair of a chronic osteochondral defect in an ovine stifle joint after 1 year. We further hypothesized that resulting histological results would be comparable with those of chondrocyte-seeded matrix-associated autologous chondrocyte transplantation (MACT). Study Design: Controlled laboratory study. Methods: Predifferentiation period of ovine MSC within collagen gel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, 2 osteochondral lesions (7-mm diameter) were created at the medial femoral condyles of the hind legs in 9 sheep. Implantation of MSC gels was performed 6 weeks after defect creation. Thirty-six defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated MSC gels (pre-MSC gels), (2) undifferentiated MSC gels (un-MSC gels), (3) MACT gels, and (4) untreated controls (UC). Histological, immunohistochemical, and radiological evaluations followed after 12 months. Results: After 12 months in vivo, pre-MSC gels showed significantly better histological outcome compared with un-MSC gels and UC. Compared with MACT gels, the overall scores were higher for O’Driscoll and International Cartilage Repair Society (ICRS). The repair tissue of the pre-MSC group showed immunohistochemical detection of interzonal collagen type II staining. Radiological evaluation supported superior bonding of pre-MSC gels to perilesional native cartilage. Compared with previous work by our group, no degradation of the repair tissue between 6 and 12 months in vivo, particularly in pre-MSC gels, was observed. Conclusion: Repair of chronic osteochondral defects with collagen hydrogels composed of chondrogenically predifferentiated MSC shows no signs of degradation after 1 year in vivo. In addition, pre-MSC gels lead to partially superior histological results compared with articular chondrocytes. Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects without donor site morbidity by harvesting articular chondrocytes.