期刊
BIOMATERIALS ADVANCES
卷 139, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bioadv.2022.213035
关键词
Cardiomyocytes; Lactate; Induced pluripotent stem cells; Cell cycle; Cardiac tissue engineering; Metabolic environment
资金
- European Regional Development Fund (FEDER)
- Spanish Ministry of Science and Innovation (MICINN) [MICINN BES-2015-071997, MAT2015-62725-ERC, RTI2018-096320-B-C21]
- Spanish network of cell therapy (TERCEL)
- Programme/Generalitat de Catalunya [2017-SGR-359]
- Severo Ochoa Programme of the Spanish Ministry of Science and Innovation (MICINN-Grant) [SEV-2014-0425, CEX2018-000789-S]
- National Heart, Lung, and Blood Institute of the National Institutes of Health [HL135464]
- American Heart Association [19IPLOI34660342]
- Daniel Bravo Andreu Private Foundation
- CIBER
- European Commission-Euronanomed nAngioderm Project [JTC2018-103]
This study evaluated the use of lactate in in situ tissue engineering strategies for cardiac regeneration. The results showed that lactate can increase cardiomyocyte cell cycle activity and modulate the function of cardiac fibroblasts and ex vivo heart culture. These findings provide new insights into the application of lactate in cardiac regeneration.
In situ tissue engineering strategies are a promising approach to activate the endogenous regenerative potential of the cardiac tissue helping the heart to heal itself after an injury. However, the current use of complex reprogramming vectors for the activation of reparative pathways challenges the easy translation of these therapies into the clinic. Here, we evaluated the response of mouse neonatal and human induced pluripotent stem cell-derived cardiomyocytes to the presence of exogenous lactate, thus mimicking the metabolic environment of the fetal heart. An increase in cardiomyocyte cell cycle activity was observed in the presence of lactate, as determined through Ki67 and Aurora-B kinase. Gene expression and RNA-sequencing data revealed that cardiomyocytes incubated with lactate showed upregulation of BMP10, LIN28 or TCIM in tandem with downregulation of GRIK1 or DGKK among others. Lactate also demonstrated a capability to modulate the production of inflammatory cytokines on cardiac fibroblasts, reducing the production of Fas, Fraktalkine or IL-12p40, while stimulating IL-13 and SDF1a. In addition, the generation of a lactate-rich environment improved ex vivo neonatal heart culture, by affecting the contractile activity and sarcomeric structures and inhibiting epicardial cell spreading. Our results also suggested a common link between the effect of lactate and the activation of hypoxia signaling pathways. These findings support a novel use of lactate in cardiac tissue engineering, modulating the metabolic environment of the heart and thus paving the way to the development of lactate-releasing platforms for in situ cardiac regeneration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据