Enhancing Cardiomyocyte Purity through Lactate-Based Metabolic Selection
10.1007/s13770-024-00696-4
- Author:
Seung Ju SEO
1
;
Yoonhee JIN
Author Information
1. Department of Physiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2025;22(2):249-260
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND:Direct reprogramming of fibroblasts into chemically induced cardiomyocyte-like cells (CiCMs) through small molecules presents a promising cell source for cardiac regeneration and therapeutic development. However, the contaminating non-cardiomyocytes, primarily unconverted fibroblasts, reduce the effectiveness of CiCMs in various applications. This study investigated a metabolic selection approach using lactate to enrich CiCMs by exploiting the unique metabolic capability of cardiomyocytes to utilize lactate as an alternative energy source.
METHODS:Primary mouse embryonic fibroblasts (pMEFs) were reprogrammed into CiCMs and subjected to a glucosedepleted, lactate-supplemented medium for 4 days. Afterward, cell viability was analyzed, and cardiomyocyte efficiency was assessed through the expression of cardiac-specific markers. Additionally, electrophysiological function was evaluated by examining drug-induced responses.
RESULTS:The lactate treatment led to a significant decrease in the viability of non-cardiomyocytes (pMEF-LAC), while CiCMs (CiCM-LAC) showed minimal cell death. Specifically, the expression of all cardiac-related markers was increased in CiCM-LAC. Metabolically purified CiCMs exhibited enhanced contractile force and increased contraction frequency compared to non-purified CiCMs, as well as an elevated responsiveness to drugs.
CONCLUSION:This study demonstrates that lactate-based metabolic selection is an effective and practical approach for enriching CiCMs, offering a cost-effective alternative to other purification methods. The application of this strategy could potentially broaden the accessibility and utility of reprogrammed cardiomyocytes in cardiac regeneration and therapeutic development.
