Católica Biomedical Research Centre, Católica Medical School, Universidade Católica Portuguesa, 1649-023 Lisbon, Portugal.
Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.
Int J Mol Sci. 2023 Jul 25;24(15):11933. doi: 10.3390/ijms241511933.
Human pluripotent stem cells (PSCs), which include both embryonic and induced pluripotent stem cells, are widely used in fundamental and applied biomedical research. They have been instrumental for better understanding development and cell differentiation processes, disease origin and progression and can aid in the discovery of new drugs. PSCs also hold great potential in regenerative medicine to treat or diminish the effects of certain debilitating diseases, such as degenerative disorders. However, some concerns have recently been raised over their safety for use in regenerative medicine. One of the major concerns is the fact that PSCs are prone to errors in passing the correct number of chromosomes to daughter cells, resulting in aneuploid cells. Aneuploidy, characterised by an imbalance in chromosome number, elicits the upregulation of different stress pathways that are deleterious to cell homeostasis, impair proper embryo development and potentiate cancer development. In this review, we will summarize known molecular mechanisms recently revealed to impair mitotic fidelity in human PSCs and the consequences of the decreased mitotic fidelity of these cells. We will finish with speculative views on how the physiological characteristics of PSCs can affect the mitotic machinery and how their suboptimal mitotic fidelity may be circumvented.
人类多能干细胞（PSCs）包括胚胎干细胞和诱导多能干细胞，广泛应用于基础和应用生物医学研究。它们在更好地理解发育和细胞分化过程、疾病起源和进展以及帮助发现新药方面发挥了重要作用。PSCs 在再生医学中也具有很大的潜力，可以治疗或减轻某些使人衰弱的疾病的影响，如退行性疾病。然而，最近人们对它们在再生医学中的使用安全性提出了一些担忧。其中一个主要问题是 PSCs 容易在将正确数量的染色体传递给子细胞时出错，导致非整倍体细胞。非整倍体的特点是染色体数量失衡，引发不同的应激途径上调，对细胞内稳态有害，损害胚胎的正常发育，并促进癌症的发展。在这篇综述中，我们将总结最近发现的影响人 PSCs 有丝分裂保真度的已知分子机制，以及这些细胞有丝分裂保真度降低的后果。最后，我们将对 PSCs 的生理特征如何影响有丝分裂机制以及如何规避其有丝分裂保真度不佳进行推测。
