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Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair
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 limi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221121/ https://www.ncbi.nlm.nih.gov/pubmed/30058138 http://dx.doi.org/10.1002/term.2741 |
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author | Takahashi, Takumi Sato, Masato Toyoda, Eriko Maehara, Miki Takizawa, Daichi Maruki, Hideyuki Tominaga, Ayako Okada, Eri Okazaki, Ken Watanabe, Masahiko |
author_facet | Takahashi, Takumi Sato, Masato Toyoda, Eriko Maehara, Miki Takizawa, Daichi Maruki, Hideyuki Tominaga, Ayako Okada, Eri Okazaki, Ken Watanabe, Masahiko |
author_sort | Takahashi, Takumi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6221121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62211212018-11-15 Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair Takahashi, Takumi Sato, Masato Toyoda, Eriko Maehara, Miki Takizawa, Daichi Maruki, Hideyuki Tominaga, Ayako Okada, Eri Okazaki, Ken Watanabe, Masahiko J Tissue Eng Regen Med Research Articles 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. John Wiley and Sons Inc. 2018-08-14 2018-10 /pmc/articles/PMC6221121/ /pubmed/30058138 http://dx.doi.org/10.1002/term.2741 Text en © 2018 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Takahashi, Takumi Sato, Masato Toyoda, Eriko Maehara, Miki Takizawa, Daichi Maruki, Hideyuki Tominaga, Ayako Okada, Eri Okazaki, Ken Watanabe, Masahiko Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title | Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title_full | Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title_fullStr | Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title_full_unstemmed | Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title_short | Rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
title_sort | rabbit xenogeneic transplantation model for evaluating human chondrocyte sheets used in articular cartilage repair |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221121/ https://www.ncbi.nlm.nih.gov/pubmed/30058138 http://dx.doi.org/10.1002/term.2741 |
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