Imperial College London
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Emeritus ProfessorKenMacLeod

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor of Cardiac Physiology
 
 
 
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Contact

 

+44 (0)20 7594 2734k.t.macleod

 
 
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Assistant

 

Miss Natasha Richmond +44 (0)20 7594 6457

 
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Location

 

336ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Dark:2023:10.1016/j.crmeth.2023.100456,
author = {Dark, N and Cosson, M-V and Tsansizi, LI and Owen, TJ and Ferraro, E and Francis, AJ and Tsai, S and Bouissou, C and Weston, A and Collinson, L and Abi-Gerges, N and Miller, PE and MacLeod, KT and Ehler, E and Mitter, R and Harding, SE and Smith, JC and Bernardo, AS},
doi = {10.1016/j.crmeth.2023.100456},
journal = {Cell Reports: Methods},
title = {Generation of left ventricle-like cardiomyocytes with improved structural, functional, and metabolic maturity from human pluripotent stem cells},
url = {http://dx.doi.org/10.1016/j.crmeth.2023.100456},
volume = {3},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Decreased left ventricle (LV) function caused by genetic mutations or injury often leads to debilitating and fatal cardiovascular disease. LV cardiomyocytes are, therefore, a potentially valuable therapeutical target. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are neither homogeneous nor functionally mature, which reduces their utility. Here, we exploit cardiac development knowledge to instruct differentiation of hPSCs specifically toward LV cardiomyocytes. Correct mesoderm patterning and retinoic acid pathway blocking are essential to generate near-homogenous LV-specific hPSC-CMs (hPSC-LV-CMs). These cells transit via first heart field progenitors and display typical ventricular action potentials. Importantly, hPSC-LV-CMs exhibit increased metabolism, reduced proliferation, and improved cytoarchitecture and functional maturity compared with age-matched cardiomyocytes generated using the standard WNT-ON/WNT-OFF protocol. Similarly, engineered heart tissues made from hPSC-LV-CMs are better organized, produce higher force, and beat more slowly but can be paced to physiological levels. Together, we show that functionally matured hPSC-LV-CMs can be obtained rapidly without exposure to current maturation regimes.
AU  - Dark,N
AU  - Cosson,M-V
AU  - Tsansizi,LI
AU  - Owen,TJ
AU  - Ferraro,E
AU  - Francis,AJ
AU  - Tsai,S
AU  - Bouissou,C
AU  - Weston,A
AU  - Collinson,L
AU  - Abi-Gerges,N
AU  - Miller,PE
AU  - MacLeod,KT
AU  - Ehler,E
AU  - Mitter,R
AU  - Harding,SE
AU  - Smith,JC
AU  - Bernardo,AS
DO  - 10.1016/j.crmeth.2023.100456
PY  - 2023///
SN  - 2667-2375
TI  - Generation of left ventricle-like cardiomyocytes with improved structural, functional, and metabolic maturity from human pluripotent stem cells
T2  - Cell Reports: Methods
UR  - http://dx.doi.org/10.1016/j.crmeth.2023.100456
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000987259100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://doi.org/10.1016/j.crmeth.2023.100456
UR  - http://hdl.handle.net/10044/1/107369
VL  - 3
ER  -
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