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Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair
Author(s) -
Takahashi Takumi,
Sato Masato,
Toyoda Eriko,
Maehara Miki,
Takizawa Daichi,
Maruki Hideyuki,
Tominaga Ayako,
Okada Eri,
Okazaki Ken,
Watanabe Masahiko
Publication year - 2018
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.2741
Subject(s) - fibrocartilage , hyaline cartilage , transplantation , chondrocyte , cartilage , regeneration (biology) , medicine , immunosuppression , articular cartilage repair , tacrolimus , hyaline , pathology , articular cartilage , surgery , osteoarthritis , immunology , anatomy , biology , microbiology and biotechnology , alternative medicine
Research on cartilage regeneration has developed novel sources for human chondrocytes and new regenerative therapies, but appropriate animal models for translational research are needed. Although rabbit models are frequently used in such studies, the availability of immunocompromised rabbits is limited. Here, we investigated the usefulness of an immunosuppressed rabbit model to evaluate directly the efficacy of human chondrocyte sheets through xenogeneic transplantation. Human chondrocyte sheets were transplanted into knee osteochondral defects in Japanese white rabbits administered with immunosuppressant tacrolimus at a dosage of 0.8 or 1.6 mg/kg/day for 4 weeks. Histological evaluation at 4 weeks after transplantation in rabbits administered 1.6 mg/kg/day showed successful engraftment of human chondrocytes and cartilage regeneration involving a mixture of hyaline cartilage and fibrocartilage. No human chondrocytes were detected in rabbits administered 0.8 mg/kg/day, although regeneration of hyaline cartilage was confirmed. Histological evaluation at 12 weeks after transplantation (i.e., 8 weeks after termination of immunosuppression) showed strong immune rejection of human chondrocytes, which indicated that, even after engraftment, articular cartilage is not particularly immune privileged in xenogeneic transplantation. Our results suggest that Japanese white rabbits administered tacrolimus at 1.6 mg/kg/day and evaluated at 4 weeks may be useful as a preclinical model for the direct evaluation of human cell‐based therapies.