Callaghan Neal I, Durland Lauren J, Ireland Ronald G, Santerre J Paul, Simmons Craig A, Davenport Huyer Locke
Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, M5G 1M1, Canada.
Institute of Biomedical Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.
NPJ Regen Med. 2022 Sep 3;7(1):44. doi: 10.1038/s41536-022-00246-3.
The development of induced-pluripotent stem cell (iPSC)-derived cell types offers promise for basic science, drug testing, disease modeling, personalized medicine, and translatable cell therapies across many tissue types. However, in practice many iPSC-derived cells have presented as immature in physiological function, and despite efforts to recapitulate adult maturity, most have yet to meet the necessary benchmarks for the intended tissues. Here, we summarize the available state of knowledge surrounding the physiological mechanisms underlying cell maturation in several key tissues. Common signaling consolidators, as well as potential synergies between critical signaling pathways are explored. Finally, current practices in physiologically relevant tissue engineering and experimental design are critically examined, with the goal of integrating greater decision paradigms and frameworks towards achieving efficient maturation strategies, which in turn may produce higher-valued iPSC-derived tissues.
诱导多能干细胞（iPSC）衍生细胞类型的发展为基础科学、药物测试、疾病建模、个性化医疗以及多种组织类型的可转化细胞疗法带来了希望。然而，在实践中，许多iPSC衍生细胞在生理功能上表现为不成熟，尽管人们努力重现成年期的成熟状态，但大多数细胞仍未达到预期组织所需的基准。在这里，我们总结了围绕几种关键组织中细胞成熟的生理机制的现有知识状态。探讨了常见的信号整合因子以及关键信号通路之间的潜在协同作用。最后，对生理相关组织工程和实验设计中的当前实践进行了批判性审视，目标是整合更多的决策范式和框架，以实现有效的成熟策略，进而可能产生更有价值的iPSC衍生组织。
