A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
Department of Neurosurgery, Kuopio University Hospital, 70029 Kuopio, Finland.
Cells. 2021 Dec 29;11(1):106. doi: 10.3390/cells11010106.
Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize MEA results from the human brain and compare them to the literature on MEA recordings of hPSC-derived brain models. MEA recordings have shown network activity in two-dimensional hPSC-derived brain models that is comparable to the human brain and revealed pathology-associated changes in disease models. Three-dimensional hPSC-derived models such as brain organoids possess a more relevant microenvironment, tissue architecture and potential for modeling the network activity with more complexity than two-dimensional models. hPSC-derived brain models recapitulate many aspects of network function in the human brain and provide valid disease models, but certain advancements in differentiation methods, bioengineering and available MEA technology are needed for these approaches to reach their full potential.
人多能干细胞（hPSC）衍生的神经元培养物已成为人类大脑电活动的模型。微电极阵列（MEA）测量细胞培养物或组织的细胞外电势能的变化，并能够记录神经元网络活动。MEA 已应用于人体和 hPSC 衍生的脑模型。在这里，我们回顾了使用 MEA 对 hPSC 衍生的二维和三维脑模型进行功能表征的文献，并研究了它们在生理和病理环境下的网络功能。我们还总结了来自人类大脑的 MEA 结果，并将其与关于 MEA 记录的 hPSC 衍生脑模型的文献进行了比较。MEA 记录显示，二维 hPSC 衍生脑模型中的网络活动与人类大脑相当，并在疾病模型中显示出与病理学相关的变化。三维 hPSC 衍生模型，如脑类器官，具有更相关的微环境、组织架构和更复杂的网络活动建模潜力，比二维模型更复杂。hPSC 衍生的脑模型再现了人类大脑网络功能的许多方面，并提供了有效的疾病模型，但为了充分发挥这些方法的潜力，还需要在分化方法、生物工程和可用的 MEA 技术方面取得某些进展。
