Next-Generation Metabolic Reprogramming in iPSC-Derived Cardiomyocytes: CRISPR-EV Synergy for Precision Cardiac...

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Cardiovascular Research

Background:

• Cardiovascular disease is a leading cause of death due to limited heart tissue regeneration.
• Stem cell-derived cardiomyocytes (iPSC-CMs) show promise for cardiac repair but suffer from metabolic immaturity, hindering their effectiveness.
• Metabolic reprogramming can enhance iPSC-CM function, but requires advanced strategies for optimal results.

Purpose of the Study:

• To review CRISPR-based metabolic engineering and extracellular vesicle (EV)-mediated metabolic modulation for iPSC-CM maturation.
• To highlight CRISPR-EV synergy as a systems-level strategy for enhancing cardiac cell function.
• To discuss the potential of this approach for regenerative medicine and disease modeling.

Main Methods:

• CRISPR gene editing techniques (activation, interference, epigenome editing) targeting key metabolic regulators (e.g., PGC-1α, TFAM, PPARs).
• Engineering extracellular vesicles (EVs) to deliver therapeutic molecules (miRNAs, enzymes, redox modulators) for non-genomic metabolic optimization.
• Synthesizing mechanistic insights, bioenergetic data, and translational considerations.

Main Results:

• CRISPR approaches can stably enhance mitochondrial networks and respiratory capacity in iPSC-CMs.
• Engineered EVs can optimize bioenergetic function and reduce oxidative stress in iPSC-CMs.
• The synergistic combination of CRISPR and EVs offers a precision framework for metabolic maturation.

Conclusions:

• CRISPR-EV synergy represents a novel strategy for durable metabolic maturation of iPSC-CMs.
• This approach holds significant implications for advancing cardiac regenerative therapy and pharmacologic screening.
• Enhanced iPSC-CMs could lead to more effective myocardial repair strategies.