ArticleTissue engineering and regenerative medicine2025
Enhancing Cardiomyocyte Purity through Lactate-Based Metabolic Selection.
Article in Tissue engineering and regenerative medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDirect 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.
methodsPrimary mouse embryonic fibroblasts (pMEFs) were reprogrammed into CiCMs and subjected to a glucose-depleted, 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.
resultsThe 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.
conclusionThis 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.
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