Almeida Micael, Inácio José M, Vital Carlos M, Rodrigues Madalena R, Araújo Beatriz C, Belo José A
Stem Cells and Development Laboratory, iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal.
Int J Mol Sci. 2025 Mar 27;26(7):3063. doi: 10.3390/ijms26073063.
Cardiovascular disease (CVD) remains the leading cause of death globally, with myocardial infarction (MI) being a major contributor. The current therapeutic approaches are limited in effectively regenerating damaged cardiac tissue. Up-to-date strategies for heart regeneration/reconstitution aim at cardiac remodeling through repairing the damaged tissue with an external cell source or by stimulating the existing cells to proliferate and repopulate the compromised area. Cell reprogramming is addressed to this challenge as a promising solution, converting fibroblasts and other cell types into functional cardiomyocytes, either by reverting cells to a pluripotent state or by directly switching cell lineage. Several strategies such as gene editing and the application of miRNA and small molecules have been explored for their potential to enhance cardiac regeneration. Those strategies take advantage of cell plasticity by introducing reprogramming factors that regress cell maturity in vitro, allowing for their later differentiation and thus endorsing cell transplantation, or promote in situ cell proliferation, leveraged by scaffolds embedded with pro-regenerative factors promoting efficient heart restoration. Despite notable advancements, important challenges persist, including low reprogramming efficiency, cell maturation limitations, and safety concerns in clinical applications. Nonetheless, integrating these innovative approaches offers a promising alternative for restoring cardiac function and reducing the dependency on full heart transplants.
心血管疾病(CVD)仍然是全球主要的死亡原因,心肌梗死(MI)是主要促成因素。目前的治疗方法在有效再生受损心脏组织方面存在局限性。最新的心脏再生/重构策略旨在通过外部细胞来源修复受损组织或刺激现有细胞增殖并重新填充受损区域来实现心脏重塑。细胞重编程作为一种有前景的解决方案被用于应对这一挑战,即将成纤维细胞和其他细胞类型转化为功能性心肌细胞,方法是将细胞恢复到多能状态或直接转换细胞谱系。人们已经探索了几种策略,如基因编辑以及miRNA和小分子的应用,以挖掘它们增强心脏再生的潜力。这些策略利用细胞可塑性,通过引入在体外使细胞成熟度倒退的重编程因子,使其随后分化,从而支持细胞移植,或通过嵌入促进心脏有效恢复的促再生因子的支架来促进原位细胞增殖。尽管取得了显著进展,但重要挑战依然存在,包括重编程效率低、细胞成熟受限以及临床应用中的安全性问题。尽管如此,整合这些创新方法为恢复心脏功能和减少对全心脏移植的依赖提供了一个有前景的替代方案。
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