In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells
In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells
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人诱导多能干细胞来源的间充质干细胞通过神经嵴细胞体内再生大鼠喉软骨
DOI：
10.1016/j.scr.2021.102233
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发表时间：
2021
影响因子：
1.2
通讯作者：
Koichi Omori
中科院分区：
文献类型：
--
作者：
Masayoshi Yoshimatsu;Hiroe Ohnishi;Chengzhu Zhao;Yasuyuki Hayashi;Fumihiko Kuwata;Shinji Kaba;Hideaki Okuyama;Yoshitaka Kawai;Nao Hiwatashi;Yo Kishimoto;Tatsunori Sakamoto;Makoto Ikeya;Koichi Omori
喉气管软骨是维持气道呼吸的基本框架，偶尔需要重建。由于透明软骨本身的再生能力较差，人们尝试了各种再生方法来再生喉气管软骨。自体间充质干细胞（MSCs）用于软骨再生已被广泛研究。然而，长期培养可能会限制增殖能力。人类诱导的多能干细胞衍生的间充质干细胞（iMSCs）由于其无限的增殖能力可以避免这个问题。本研究旨在探讨骨髓间充质干细胞在免疫缺陷大鼠甲状腺软骨再生中的作用。本研究通过神经嵴细胞中间体诱导间充质干细胞。为了与未来的临床应用相关，在无xeno /无血清的条件下进行诱导。然后，将iMSC/细胞外基质复合物（C-iMSC）制备的团块移植到免疫缺陷大鼠甲状腺软骨缺损中。组织学检查显示再生病灶内有软骨样再生组织和人核抗原（HNA）阳性的移植存活细胞。hna阳性细胞共表达SOX9，在hna阳性细胞周围发现II型胶原。这些结果表明，移植的C-iMSCs促进了甲状腺软骨的再生，部分iMSCs分化为软骨谱系细胞。诱导间充质干细胞可能是一种很有前途的用于人喉气管重建的候选细胞疗法。
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.