Enhancing Cardiomyocyte Purity through Lactate-Based Metabolic Selection
1Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Tissue Engineering and Regenerative Medicine
|January 17, 2025
Summary
Lactate metabolic selection effectively purifies chemically induced cardiomyocyte-like cells (CiCMs) by reducing fibroblast contamination. This method enhances CiCMs
Area of Science:
- Cardiovascular Research
- Cellular Reprogramming
- Metabolic Engineering
Background:
- Direct reprogramming of fibroblasts into cardiomyocyte-like cells (CiCMs) offers potential for cardiac regeneration.
- Contamination by non-cardiomyocytes, mainly fibroblasts, limits the effectiveness of CiCMs.
- A metabolic selection strategy is needed to improve CiCM purity and function.
Purpose of the Study:
- To investigate lactate as a metabolic selection agent for enriching CiCMs.
- To assess the impact of lactate selection on CiCM viability and purity.
- To evaluate the functional improvement of lactate-purified CiCMs.
Main Methods:
- Fibroblasts were reprogrammed into CiCMs.
- Cells were cultured in glucose-depleted, lactate-supplemented medium for 4 days.
- Cell viability, cardiac marker expression, and electrophysiological function were assessed.
Main Results:
- Lactate treatment significantly reduced non-cardiomyocyte viability while preserving CiCMs.
- Cardiac-specific marker expression was elevated in lactate-treated CiCMs (CiCM-LAC).
- Purified CiCMs demonstrated enhanced contractile force, contraction frequency, and drug responsiveness.
Conclusions:
- Lactate-based metabolic selection is an effective and practical method for enriching CiCMs.
- This approach offers a cost-effective alternative to existing purification techniques.
- Enriched CiCMs hold promise for advancing cardiac regeneration and therapeutic applications.
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