In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

Stem Cell Research

Tatsunori Sakamoto¹  Koichi Omori²  Chengzhu Zhao²  Nao Hiwatashi³  Fumihiko Kuwata⁴  Masayoshi Yoshimatsu⁴  Hiroe Ohnishi⁴  Yoshitaka Kawai⁴  Yo Kishimoto⁴  Shinji Kaba⁴  Yasuyuki Hayashi⁴  Hideaki Okuyama⁴  Makoto Ikeya⁵ 

[1] Corresponding author at: Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.;Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan;Department of Otolaryngology, Kyoto-Katsura Hospital, Kyoto, Japan;Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan;Department of Otorhinolaryngology, Shimane University Faculty of Medicine, Shimane, Japan;

关键词: Human iPS cells;    Regeneration;    Laryngotracheal cartilage;    Mesenchymal stem cell;    Neural crest cells;    Hyaline cartilage;   

DOI  :  

来源: DOAJ

【 摘 要 】

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction.

【 授权许可】

Unknown