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Updated: May 6, 2026

Electrophysiological Analysis of human Pluripotent Stem Cell-derived Cardiomyocytes hPSC-CMs Using Multi-electrode Arrays MEAs

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Published on: May 12, 2017

異なる薬剤によるhERGブロックによって引き起こされる遅れた再極化は,幹細胞由来心筋細胞で検出される:インキュベーション時間は重要です

Yusheng Qu¹, Wei Guo², Bin Wu³

¹Translational Safety & Bioanalytical Sciences, Amgen Research, Thousand Oaks, California, USA.

Clinical and translational science

|August 23, 2025

まとめ

ヒューマン誘発性多能幹細胞由来心肌細胞 (hiPSC-CM) モデルでは,hERG遺伝子の静止によって引き起こされる遅れた心臓再極化を検出するには48時間が必要です. この延長された時間枠は,オリゴヌクレオチドが心臓のイオンチャネルに及ぼす影響を評価するのに極めて重要です.

科学分野:

心血管薬学
幹細胞生物学
分子毒理学

背景:

従来の in vitro 心臓モデルでは,変異と拡張培養の制限により,オリゴヌクレオチドの評価に苦労します.
ヒューマン誘発性多能幹細胞由来心筋細胞 (hiPSC-CM) は,長期の薬剤評価と記録に適したプラットフォームを提供します.
以前の研究では,安定した細胞系におけるhERGに対するsiRNA効果を観察するために48時間の慢性的なプロトコルが必要であることが示されました.

研究の目的:

hERGターゲティング siRNAによって誘発されたhiPSC-CMにおける遅延した心臓再偏極化を調査する.
薬によるhERGチャネル機能障害とsiRNAによるhERGチャネル機能障害の時間経過を比較する.
心臓の電気生理学に対する遺伝子静止効果の最適な評価時間を確立する.

主な方法:

フィールドポテンシャル (FP) は,hiPSC- CMで多電極配列 (MEA) を使用して記録された.
モキシフロクサシンとペンタミディンの暴露は,FPDの期間に対する急性薬剤効果を評価した.
mRNA発現とFPDを様々な時間点 (6, 24, 48時間) でモニタリングした.

主要な成果:

ペンタミディンは24時間必要でした.
hERG siRNAはmRNAの発現を6時間減少させた.
タンパク質の周回時間を示す48時間での最大効果で,トランスフェクション後の24時間の間に重要なFPD延長が観察されました.

結論:

hiPSC-CMでのMEA記録は,hERGに影響する様々なメカニズムによる心臓再偏極化の障害を検出することができます.
メカニズムには,直接的なチャネル遮断,タンパク質の密輸抑制,siRNAによる遺伝子静止が含まれます.
遺伝子サイレンスによる間接的なhERGノックダウンは,遅れたリポラライゼーションを検出するために,hiPSC- CMで少なくとも48時間の治療後の評価を必要とします.

キーワード:

PCR について hERG hiPSC-CMについてマルチエレクトロッド配列オリゴヌクレオチド siRNA について

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