Modulation of cardiomyocyte electrical properties using regulated bone morphogenetic protein-2 expression.

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Gene Therapy

Background:

• Cardiomyocytes lack regenerative capacity post-birth, leading to cardiac dysfunction.
• Restoring cardiomyocyte electrophysiological activity is key for cardiac tissue regeneration.
• Existing methods lack precise control over gene expression for therapeutic interventions.

Purpose of the Study:

• To investigate the regulation of cardiomyocyte electrophysiological characteristics using inducible gene expression.
• To assess the potential of engineered cardiac microtissues for restoring cardiac function.
• To demonstrate controlled gene delivery for therapeutic applications in cardiac regeneration.

Main Methods:

• Utilized lentivirus-derived particles for inducible bone morphogenetic protein-2 (BMP-2) gene expression.
• Employed complementary metal oxide semiconductor-based high-density microelectrode arrays (HD-MEAs) to monitor cardiomyocyte electrophysiology.
• Cultured neonatal rat cardiomyocytes (NRCs) as monolayers (NRCml) and microtissues (NRCmt), with NRCmt mimicking heart tissue physiology.

Main Results:

• Inducible BMP-2 expression successfully adjusted cardiomyocyte electrophysiological characteristics.
• Engineered cardiomyocyte microtissues (NRCmt) restored myocardial electrical activity.
• NRCmt exhibited pacemaker-like activity when functionally coupled and regulated for BMP-2 expression.

Conclusions:

• Controlled transgene expression via lentiviral vectors is a viable strategy for cardiac regeneration.
• Cardiac microtissues monitored by HD-MEAs provide a physiologically relevant model for studying cardiac electrophysiology.
• This approach advances gene-function analysis and holds potential for clinical interventions in heart disease.