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Atelocollagen-Embedded Chondrocyte Precursors as a Treatment for Grade-4 Cartilage Defects of the Femoral Condyle: A Case Series with up to 9-Year Follow-Up.

ABSTRACT: We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. Neotissues made of CPs were implanted into cartilage defects with an average cell density of 4.9 ± 2.1 × 10⁶ cells/cm² through arthrotomy. The knee function was evaluated with the International Knee Documentation Committee (IKDC) subjective knee form. Patients' knee functions significantly improved by the 28th week (IKDC score = 68.3 ± 12.1), relative to the initial functionality before the CP therapy (IKDC score = 46.1 ± 16.4, p-value = 0.0014). Nine of these twelve patients maintained good knee functions for 9 years post-implantation (IKDC score = 69.8 ± 12.3) at levels higher than the pre-implantation values (p-value = 0.0018). Patients were evaluated with MRI and arthroscopy, and the defective sites exhibited a smooth surface without a gap between the implant and host tissue. This study demonstrates that autologous CPs successfully engraft into the host tissue and result in the re-formation of hyaline-like cartilage, thereby improving the impaired knee functions. Most importantly, no adverse event was reported during this long-term follow-up period.

SUBMITTER: Liu HC

PROVIDER: S-EPMC8301975 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Anterior cruciate ligament injuries result in posttraumatic osteoarthritis in the medial compartment of the knee, even after surgical treatment. How the chondrocyte distribution within the articular cartilage changes early in this process is currently unknown. The study objective was to investigate the chondrocyte distribution within the medial femoral condyle after an anterior cruciate ligament transection in a preclinical model. Forty-two adolescent Yucatan minipigs were allocated to receive unilateral anterior cruciate ligament surgery (n = 36) or no surgery (n = 6). Central coronal sections of the medial femoral condyle were obtained at 1- and 4 weeks after surgery, and the chondrocyte distribution was measured via whole slide imaging and a cell counting batch processing tool utilized in ImageJ. Ki-67 immunohistochemistry was performed to identify proliferating cells. Empty lacunae, karyolysis, karyorrhexis, and pyknosis were used to identify areas of irreversible cell injury. The mean area of irreversible cell injury was 0% in the intact controls, 13.4% (95% confidence interval: 6.4, 20.3) at 1-week post-injury and 19.3% (9.7, 28.9) at 4 weeks post-injury (p < .015). These areas occurred closest to the femoral intra-articular notch. The remaining areas containing viable chondrocytes had Ki-67-positive cells (p < .02) and increased cell density in the middle (p < .03) and deep zones (p = .001). For the entire section, the total chondrocyte number did not change significantly post-operatively; however, the density of cells in the peripheral regions of the medial femoral condyle increased significantly at 1- and 4 weeks post-injury relative to the intact control groups (p = .032 and .004, respectively). These data demonstrate a peripheral shift in the viable chondrocyte population of the medial femoral condyle after anterior cruciate ligament injury and further suggest that chondrocytes with the capacity to proliferate are not confined to one particular cartilage layer.

Dataset Information

Atelocollagen-Embedded Chondrocyte Precursors as a Treatment for Grade-4 Cartilage Defects of the Femoral Condyle: A Case Series with up to 9-Year Follow-Up.

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