Abstract
BackgroundWe previously conducted a first-in-human clinical study of articular cartilage repair using autologous chondrocyte sheets and confirmed the regeneration of hyaline-like cartilage in all eight patients. However, regenerative medicine with autologous chondrocyte sheets requires the harvesting of tissue from healthy regions, and the quality of this tissue varies between individuals. To overcome such limitations, allogeneic transplantation is a promising treatment method, particularly for articular cartilage repair. In this study, we investigated the characteristics of polydactyly-derived chondrocyte sheets fabricated from the chondrocytes of young polydactyly donors.MethodsPolydactyly-derived chondrocyte (PD) sheets were fabricated from the tissue obtained from eight polydactyly donors (average age = 13.4 months). To create these PD sheets, chondrocytes at passage 2 or 3 were seeded on temperature-responsive culture inserts and cultured for 2 weeks. For comparison, adult chondrocyte sheets were fabricated from tissue obtained from 11 patients who underwent total knee arthroplasty (TKA; average age = 74 years). To create these TKA sheets, chondrocytes and synovial cells were cocultured, and the chondrocyte sheets were triple-layered according to the protocol from our previous clinical study. Cell count, cell viability, cell surface markers, cell histology, and humoral factors secreted by the sheets were characterized and compared between the PD sheets and TKA sheets.ResultsPolydactyly-derived chondrocytes proliferated rapidly to establish a layered structure with sufficient extracellular matrix and formed sheets that could be easily manipulated without tearing. Similar to TKA sheets, PD sheets expressed aggrecan and fibronectin at the protein level and the surface markers CD44, CD81, and CD90, which are characteristic of mesenchymal cells. PD sheets also produced significantly higher levels of transforming growth factor beta-1 and lower levels of matrix metalloproteinase-3 than those produced by TKA sheets, suggesting that young polydactyly-derived chondrocytes have advantages as a potential cell source.ConclusionsPD sheets exhibited characteristics thought to be important to chondrocyte sheets as well as proliferative capacity that may facilitate provision of a stable supply in the future.
Highlights
We previously conducted a first-in-human clinical study of articular cartilage repair using autologous chondrocyte sheets and confirmed the regeneration of hyaline-like cartilage in all eight patients
Isolation and proliferation of Polydactyly-derived chondrocyte (PD) The average wet weight of cartilage tissue obtained from polydactyly donors was 0.3 g, and the average number of cells collected after enzymatic digestion was 0.17 × 106 cells (Table 1)
Only 1 to 3 g of cartilage tissue was collected during the clinical trial; the number of autologous chondrocyte sheets that were fabricated in the clinical trial was three to seven sheets
Summary
We previously conducted a first-in-human clinical study of articular cartilage repair using autologous chondrocyte sheets and confirmed the regeneration of hyaline-like cartilage in all eight patients. Regenerative medicine with autologous chondrocyte sheets requires the harvesting of tissue from healthy regions, and the quality of this tissue varies between individuals. To overcome such limitations, allogeneic transplantation is a promising treatment method, for articular cartilage repair. Because of its low cellularity and avascular nature, its capacity to selfregenerate after injury or degeneration is limited [1] Existing treatment methods such as subchondral drilling [2], microfracture [3, 4], and mosaicplasty [5, 6] are all symptomatic therapies that typically fill defects with inferior fibrocartilage, which lacks the mechanical properties exhibited by native hyaline cartilage. Regeneration of hyaline cartilage is a challenge for regenerative medicine and is considered important in providing a long-term treatment
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