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KAKEN_19K22626seika.pdf
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Title |
Title |
ヒトiPS細胞由来高純度心室筋細胞移植における催不整脈作用機序の解明
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ヒト iPS サイボウ ユライ コウジュンド シンシツキン サイボウ イショク ニ オケル サイフセイミャク サヨウ キジョ ノ カイメイ
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Hito iPS saibō yurai kōjundo shinshitsukin saibō ishoku ni okeru saifuseimyaku sayō kijo no kaimei
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Evaluation of post-transplant arrhythmia in human iPSC-derived purified ventricular cardiomyocytes
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遠山, 周吾
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トオヤマ, シュウゴ
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Tōyama, Shūgo
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慶應義塾大学・医学部 (信濃町) ・講師
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Research team head
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科研費研究者番号 : 90528192
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柴, 祐司
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シバ, ユウジ
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Shiba, Yūji
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信州大学・学術研究院医学系・教授
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Research team member
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科研費研究者番号 : 70613503
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2021
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科学研究費補助金研究成果報告書
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2020
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ヒトiPS細胞は心筋細胞を含むさまざまな細胞へ分化することができるため、再生医療への応用が期待されているが、心臓再生医療を実現化するためには、移植後の催不整脈作用という課題を克服しなければならない。そこで、申請者は臨床用のHLAホモ接合体ヒトiPS細胞から臨床グレードの培養システムにより高純度心室筋細胞を作製した。その後、微小組織球を作製した後、カニクイザル心筋梗塞モデルに免疫抑制剤投与下で移植し、催不整脈作用および心機能を評価した。その結果、長期生着を維持しながら、心機能は有意に改善し、心室頻拍のリスクは極めて低いことが示され、高純度心室筋細胞が極めて安全性の高い細胞であることがわかった。
Since human iPSCs can differentiate into various types of cells including cardiomyocytes, they are expected to be applied to regenerative medicine. However, to realize cardiac regenerative medicine, there is a risk of post-transplant arrhythmia. Therefore, we prepared purified ventricular cardiomyocytes from clinical-grade HLA homozygous human iPSCs by our developed clinical-grade culture system. Then, after production of cardiac spheroids, they were transplanted into cynomolgus monkey myocardial infarction models under immunosuppressive drug administration, and post-transplant arrhythmia and cardiac function were evaluated. As a result, we observed long-term engraftment of cardiac tissue and demonstrated that cardiac function was significantly improved and the risk of ventricular tachycardia was extremely low. Therefore, the transplanted purified ventricular cardiomyocytes were suitable for safer transplantation.
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研究種目 : 挑戦的研究 (萌芽)
研究期間 : 2019~2020
課題番号 : 19K22626
研究分野 : 再生医学
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