LAAS-CNRS, Université de Toulouse, CNRS, Toulouse, F-31400, France.
Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, P.O. Box 100, Lebanon.
Adv Healthc Mater. 2024 May;13(13):e2303288. doi: 10.1002/adhm.202303288. Epub 2024 Feb 20.
Cardiovascular diseases are a leading cause of mortality and pose a significant burden on healthcare systems worldwide. Despite remarkable progress in medical research, the development of effective cardiovascular drugs has been hindered by high failure rates and escalating costs. One contributing factor is the limited availability of mature cardiomyocytes (CMs) for accurate disease modeling and drug screening. Human induced pluripotent stem cell-derived CMs offer a promising source of CMs; however, their immature phenotype presents challenges in translational applications. This review focuses on the road to achieving mature CMs by summarizing the major differences between immature and mature CMs, discussing the importance of adult-like CMs for drug discovery, highlighting the limitations of current strategies, and exploring potential solutions using electro-mechano active polymer-based scaffolds based on conductive polymers. However, critical considerations such as the trade-off between 3D systems and nutrient exchange, biocompatibility, degradation, cell adhesion, longevity, and integration into wider systems must be carefully evaluated. Continued advancements in these areas will contribute to a better understanding of cardiac diseases, improved drug discovery, and the development of personalized treatment strategies for patients with cardiovascular disorders.
心血管疾病是全球范围内导致死亡的主要原因之一,对医疗系统造成了重大负担。尽管医学研究取得了显著进展,但有效的心血管药物的开发仍受到高失败率和不断增加的成本的阻碍。一个促成因素是成熟心肌细胞(CMs)的可用性有限,难以进行准确的疾病建模和药物筛选。人类诱导多能干细胞衍生的 CMs 提供了一种有前途的 CMs 来源;然而,它们不成熟的表型在转化应用中带来了挑战。本综述通过总结不成熟和成熟 CMs 之间的主要差异,讨论成人样 CMs 在药物发现中的重要性,强调当前策略的局限性,并探讨基于导电聚合物的电机械活性聚合物基支架的潜在解决方案,聚焦于实现成熟 CMs 的途径。然而,必须仔细评估 3D 系统与营养交换、生物相容性、降解、细胞黏附、寿命和与更广泛系统集成之间的权衡等关键考虑因素。这些领域的持续进展将有助于更好地理解心脏疾病,改进药物发现,并为心血管疾病患者制定个性化的治疗策略。
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