Designing multicellular cardiac tissue engineering technologies for clinical translation DOI Creative Commons
Andrew Laskary, James E. Hudson, Enzo R. Porrello

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 171, P. 103612 - 103612

Published: April 29, 2025

Cardiovascular diseases remain the leading cause of death worldwide-claiming one-third all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate clinical complexity these humans. Therefore, there is a dire need for higher fidelity biological capable replicating phenotypes to inform outcomes therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged fulfill this by design three-dimensional myocardial from human pluripotent stem cells. In way, CTE serve as highly controllable variety applications-including physiological pathological modeling, drug discovery preclinical testing platforms, even direct interventions clinic. Although significant progress has been made development technologies, critical challenges necessary refinements are required derive more advanced heart technologies. review, we distill three focus areas field address: I) Generating cardiac muscle types scalable manufacturing methods, II) Engineering structure, function, analyses, III) Curating system specific application. each our areas, emphasize importance designing mimicking intricate intercellular connectivity discuss fundamental considerations that subsequently arise. We conclude highlighting cutting-edge applications use technologies modeling repair damaged diseased hearts.

Language: Английский

Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity DOI Creative Commons
Lynn Devilée, Abou Bakr M. Salama, Jessica M. Miller

et al.

npj Regenerative Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 11, 2025

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation incompletely understood. Here we show a robust pathway for new calcium signaling-based regenerative strategies. A drug screen targeting proteins involved cycling human embryonic stem cell-derived organoids (hCOs) revealed only the inhibition of L-Type Channel (LTCC) induced cell cycle. Furthermore, overexpression Ras-related associated with Diabetes (RRAD), endogenous inhibitor LTCC, cycle activity vitro, slices, and vivo. Mechanistically, LTCC by RRAD or nifedipine modulating calcineurin activity. Moreover, ectopic expression RRAD/CDK4/CCND combination vitro vivo, improved function reduced scar size post-myocardial infarction.

Language: Английский

Citations

0
Designing multicellular cardiac tissue engineering technologies for clinical translation DOI Creative Commons
Andrew Laskary, James E. Hudson, Enzo R. Porrello

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 171, P. 103612 - 103612

Published: April 29, 2025

Cardiovascular diseases remain the leading cause of death worldwide-claiming one-third all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate clinical complexity these humans. Therefore, there is a dire need for higher fidelity biological capable replicating phenotypes to inform outcomes therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged fulfill this by design three-dimensional myocardial from human pluripotent stem cells. In way, CTE serve as highly controllable variety applications-including physiological pathological modeling, drug discovery preclinical testing platforms, even direct interventions clinic. Although significant progress has been made development technologies, critical challenges necessary refinements are required derive more advanced heart technologies. review, we distill three focus areas field address: I) Generating cardiac muscle types scalable manufacturing methods, II) Engineering structure, function, analyses, III) Curating system specific application. each our areas, emphasize importance designing mimicking intricate intercellular connectivity discuss fundamental considerations that subsequently arise. We conclude highlighting cutting-edge applications use technologies modeling repair damaged diseased hearts.

Language: Английский

Citations

0