Department of Biology, University of Padova, Padova 35131, Italy.
Veneto Institute of Molecular Medicine, Padova 35129, Italy.
Development. 2023 Jun 1;150(11). doi: 10.1242/dev.201103.
Human pluripotent stem cells (hPSCs), derived from individuals or genetically modified with disease-related mutations and variants, have revolutionised studies of human disease. Researchers are beginning to exploit the extraordinary potential of stem cell technology to screen for new drugs to treat intractable diseases, ideally without side-effects. However, a major problem is that the differentiated cell types on which these models are based are immature; they resemble fetal and not adult cells. Here, we discuss the nature and hurdles of hPSC maturation, using cardiomyocytes as an example. We review methods used to induce cardiomyocyte maturation in culture and consider remaining challenges for their integration into research on human disease and drug development pipelines.
人类多能干细胞(hPSCs)来源于个体或通过与疾病相关的突变和变体进行基因修饰,彻底改变了人类疾病的研究方式。研究人员开始利用干细胞技术的巨大潜力来筛选治疗难治性疾病的新药,理想情况下没有副作用。然而,一个主要问题是,这些模型所基于的分化细胞类型不成熟;它们类似于胎儿细胞而不是成年细胞。在这里,我们以心肌细胞为例,讨论 hPSC 成熟的性质和障碍。我们回顾了在培养中诱导心肌细胞成熟的方法,并考虑了将其整合到人类疾病研究和药物开发管道中的剩余挑战。