ヒューストン大学の研究者が心臓再生の細胞治療法を初めて報告 University of Houston Researchers First to Report Cell Therapy Process for Heart Regeneration
2022-11-21 ヒューストン大学(UH)
プルキンエ細胞は、心臓の収縮と弛緩を同期して行うための電気信号を司る心臓伝導系(CCS)の特殊な細胞であり、研究者は心臓再生における別の未解明の細胞タイプを検討した。
その結果、電気信号の伝導効率を回復させ、心機能を改善させる可能性があることが示された。
研究者たちは、独自の小分子カクテルを用いて、ヒト心筋細胞株(AC16-CMsおよびiPSC-CMs)をプルキンエ様細胞へ直接初期化することに成功した。直接リプログラミングは、エピジェネティックに不安定な「可塑的」状態を細胞に作り出し、完全に分化・成熟した細胞を、異なる新しい細胞タイプに変換することを促進する技術である。
<関連情報>
- https://uh.edu/news-events/stories/2022-news-articles/november-2022/11212022-mcconnell-heart-cells-reprogram.php
- https://www.cell.com/iscience/fulltext/S2589-0042(22)01674-1#relatedArticles
心筋細胞から心臓プルキンエ様細胞への直接再プログラミング Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells
Nicole Prodan,Faheem Ershad,Arfaxad Reyes-Alcaraz,Luge Li,Brandon Mistretta,Lei Gonzalez,Zhoulyu Rao,Cunjiang Yu,Preethi H. Gunaratne,Na Li,Robert J. Schwartz,Bradley K. McConnell
iScience Published:October 20, 2022
DOI:https://doi.org/10.1016/j.isci.2022.105402
Highlights
•Small molecule treatment of human cardiomyocytes leads to Purkinje differentiation
•Small molecule differentiation results in key Purkinje gene expression
•Differentiated Purkinje cells can conduct fast electrical signals
•Differentiated Purkinje cells are comparable to native Purkinje cells
Summary
Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2 and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration.
