The Advantages, Challenges, and Future of Human-Induced Pluripotent Stem Cell Lines in Type 2 Long QT Syndrome

被引：4

作者：

Cai, Dihui ^{[1
]}

Zheng, Zequn ^{[1
,3
]}

Jin, Xiaojun ^{[1
]}

Fu, Yin ^{[1
]}

Cen, Lichao ^{[1
]}

Ye, Jiachun ^{[1
]}

Song, Yongfei ^{[2
]}

Lian, Jiangfang ^{[1
,2
]}

机构：

[1] Ningbo Univ, Lihuili Hosp, Dept Cardiovasc, Ningbo, Zhejiang, Peoples R China

[2] Ningbo Inst Innovat Combined Med & Engn, Dept Cardiovasc, Ningbo, Peoples R China

[3] Shantou Univ, Dept Cardiovasc, Affiliated Hosp 1, Med Coll, Shantou, Peoples R China

来源：

JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH | 2023年 / 16卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Human-induced pluripotent stem cells; Type 2 long QT syndrome; KCNH2; Gene editing; Precision medicine; SUDDEN CARDIAC DEATH; GENETIC MODIFIERS; I-KR; CARDIOMYOCYTES; ARRHYTHMIA; HERG; MUTATIONS; POLYMORPHISM; MATURATION; PHENOTYPE;

D O I：

10.1007/s12265-022-10298-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Type 2 long QT syndrome (LQT2) is the second most common subtype of long QT syndrome and is caused by mutations in KCHN2 encoding the rapidly activating delayed rectifier potassium channel vital for ventricular repolarization. Sudden cardiac death is a sentinel event of LQT2. Preclinical diagnosis by genetic testing is potentially life-saving. Traditional LQT2 models cannot wholly recapitulate genetic and phenotypic features; therefore, there is a demand for a reliable experimental model. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) meet this challenge. This review introduces the advantages of the hiPSC-CM model over the traditional model and discusses how hiPSC-CM and gene editing are used to decipher mechanisms of LQT2, screen for cardiotoxicity, and identify therapeutic strategies, thus promoting the realization of precision medicine for LQT2 patients.

引用

页码：209 / 220

页数：12

共 99 条

[1] MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia [J].

Abbott, GW ;

Sesti, F ;

Splawski, I ;

Buck, ME ;

Lehmann, WH ;

Timothy, KW ;

Keating, MT ;

Goldstein, SAN .

CELL, 1999, 97 (02) :175-187

[2] Most LQT2 mutations reduce Kv11.1 (hERG) current by a class 2 (trafficking-deficient) mechanism [J].

Anderson, CL ;

Delisle, BP ;

Anson, BD ;

Kilby, JA ;

Will, ML ;

Tester, DJ ;

Gong, QM ;

Zhou, ZF ;

Ackerman, MJ ;

January, CT .

CIRCULATION, 2006, 113 (03) :365-373

[3] Large-scale mutational analysis of Kv11.1 reveals molecular insights into type 2 long QT syndrome [J].

Anderson, Corey L. ;

Kuzmicki, Catherine E. ;

Childs, Ryan R. ;

Hintz, Caleb J. ;

Delisle, Brian P. ;

January, Craig T. .

NATURE COMMUNICATIONS, 2014, 5

[4] Isogenic human pluripotent stem cell pairs reveal the role of a KCNH2 mutation in long-QT syndrome [J].

Bellin, Milena ;

Casini, Simona ;

Davis, Richard P. ;

D'Aniello, Cristina ;

Haas, Jessica ;

Ward-van Oostwaard, Dorien ;

Tertoolen, Leon G. J. ;

Jung, Christian B. ;

Elliott, David A. ;

Welling, Andrea ;

Laugwitz, Karl-Ludwig ;

Moretti, Alessandra ;

Mummery, Christine L. .

EMBO JOURNAL, 2013, 32 (24) :3161-3175

[5] Expansion and patterning of cardiovascular progenitors derived from human pluripotent stem cells [J].

Birket, Matthew J. ;

Ribeiro, Marcelo C. ;

Verkerk, Arie O. ;

Ward, Dorien ;

Leitoguinho, Ana Rita ;

den Hartogh, Sabine C. ;

Orlova, Valeria V. ;

Devalla, Harsha D. ;

Schwach, Verena ;

Bellin, Milena ;

Passier, Robert ;

Mummery, Christine L. .

NATURE BIOTECHNOLOGY, 2015, 33 (09) :970-U219

[6] A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial [J].

Boyle, Michael P. ;

Bell, Scott C. ;

Konstan, Michael W. ;

McColley, Susanna A. ;

Rowe, Steven M. ;

Rietschel, Ernst ;

Huang, Xiaohong ;

Waltz, David ;

Patel, Naimish R. ;

Rodman, David .

LANCET RESPIRATORY MEDICINE, 2014, 2 (07) :527-538

[7] Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes [J].

Braam, Stefan R. ;

Tertoolen, Leon ;

van de Stolpe, Anja ;

Meyer, Thomas ;

Passier, Robert ;

Mummery, Christine L. .

STEM CELL RESEARCH, 2010, 4 (02) :107-116

[8] Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population [J].

Brink, PA ;

Crotti, L ;

Corfield, V ;

Goosen, A ;

Durrheim, G ;

Hedley, P ;

Heradien, M ;

Geldenhuys, G ;

Vanoli, E ;

Bacchini, S ;

Spazzolini, C ;

Lundquist, AL ;

Roden, DM ;

George, AL ;

Schwartz, PJ .

CIRCULATION, 2005, 112 (17) :2602-2610

[9] Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations [J].

Casini, Simona ;

Verkerk, Arie O. ;

Remme, Carol Ann .

CARDIOVASCULAR DRUGS AND THERAPY, 2017, 31 (03) :325-344

[10] Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity [J].

Chai, Sam ;

Wan, Xiaoping ;

Ramirez-Navarro, Angelina ;

Tesar, Paul J. ;

Kaufman, Elizabeth S. ;

Ficker, Eckhard ;

George, Alfred L., Jr. ;

Deschenes, Isabelle .

JOURNAL OF CLINICAL INVESTIGATION, 2018, 128 (03) :1043-1056

← 1 2 3 4 5 6 7 8 9 10 →