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.

Safety and Efficacy of Kartigen® in Treating Cartilage Defects: A Randomized, Controlled, Phase I Trial

“…They were randomly allocated into groups of Kartigen ® implantation ( n = 10) or microfracture treatment ( n = 5). Based on our previous study [ 34 ], the seeding density of CPs was 1.6–3.3 × 10 6 cells/cm 2 , and the total cell number was less than 1.32 × 10 7 cells. The schedule of study procedures and assessments is shown in Table S2 .…”

“…The manufacture of Kartigen ® was described previously [ 34 ]. In brief, cell culture was performed under standard operative procedures at the cell processing unit (CPU) of Kartigen Biomedical Inc. (Taipei, Taiwan), following the Good Tissue Practice regulations.…”

“…The chondrogenesis of MSCs can be guided using growth factors [ 31 ] or biophysical/biomechanical stimuli [ 32 ] to improve the functional properties of the derived neo-cartilage tissues, including mature matrix formation [ 29 , 33 ]. Our previous study identified a unique population of chondrocyte precursors (CPs) derived from bone marrow mesenchymal stem cells (BMSCs) during chondrogenic induction [ 34 ]. These atelocollagen-embedded CPs (Kartigen ® ) can secrete glycosaminoglycan (GAG) and collagen type II but without lacunae formation.…”

“…In this study, we selected atelocollagen because it is a low-immunogenic derivative of collagen obtained by the removal of N– and C–terminal telopeptide components [ 39 ]. Atelocollagen has been broadly applied in the regeneration of cartilage [ 34 , 40 , 41 ], intervertebral disc [ 42 ], cornea [ 43 ], periodontal tissues [ 44 ], and skin [ 45 ] to serve as a carrier for cell delivery and to provide an appropriate microenvironment for tissue regeneration.…”

“…A 9-year follow-up trial demonstrated that Kartigen ® integrated with the host tissue and resulted in the formation of hyaline-like cartilage, thereby improving the impaired knee functions [ 34 ]. Due to the lack of a randomized control group in the previous study, we initiated this controlled and randomized trial to evaluate the safety and efficacy of Kartigen for repairing cartilage defects in the weight-bearing site of medial femoral condyles through the comparison with the microfracture treatment.…”