Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells

Keisuke Mizuno; Hiroe Ohnishi; Masayoshi Yoshimatsu; Chengzhu Zhao; Yasuyuki Hayashi; Fumihiko Kuwata; Shinji Kaba; Hideaki Okuyama; Yoshitaka Kawai; Nao Hiwatashi; Yo Kishimoto; Tatsunori Sakamoto; Makoto Ikeya; Koichi Omori

doi:10.1177/09636897231178460

Cell Transplantation (Jun 2023)

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells

Keisuke Mizuno,
Hiroe Ohnishi,
Masayoshi Yoshimatsu,
Chengzhu Zhao,
Yasuyuki Hayashi,
Fumihiko Kuwata,
Shinji Kaba,
Hideaki Okuyama,
Yoshitaka Kawai,
Nao Hiwatashi,
Yo Kishimoto,
Tatsunori Sakamoto,
Makoto Ikeya,
Koichi Omori

Affiliations

Keisuke Mizuno: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Hiroe Ohnishi: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Masayoshi Yoshimatsu: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Chengzhu Zhao: Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing, China
Yasuyuki Hayashi: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Fumihiko Kuwata: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Shinji Kaba: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Hideaki Okuyama: School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada
Yoshitaka Kawai: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Nao Hiwatashi: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Yo Kishimoto: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Tatsunori Sakamoto: Department of Otorhinolaryngology, Faculty of Medicine, Shimane University, Matsue, Japan
Makoto Ikeya: Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
Koichi Omori: Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

DOI: https://doi.org/10.1177/09636897231178460
Journal volume & issue: Vol. 32

Abstract

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Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression.

Published in Cell Transplantation

ISSN: 0963-6897 (Print); 1555-3892 (Online)
Publisher: SAGE Publishing
Country of publisher: United States
LCC subjects: Medicine
Website: http://journals.sagepub.com/home/cll

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