Hiraiwa Tsuyoshi, Yoshii Shoko, Kawada Jiro, Sugawara Tohru, Kawasaki Tomoyuki, Shibata Shinsuke, Shindo Tomoko, Fujimori Keiya, Umezawa Akihiro, Akutsu Hidenori
Department of Obstetrics and Gynecology, Fukushima Medical University, Fukushima, Japan.
Center for Regenerative Medicine, National Center for Child Health and Development, Tokyo, Japan.
Regen Ther. 2025 Mar 13;29:100-107. doi: 10.1016/j.reth.2025.02.014. eCollection 2025 Jun.
Cerebral white matter injuries, such as periventricular leukomalacia, are major contributors to neurodevelopmental impairments in preterm infants. Despite the clinical significance of these conditions, human-relevant models for studying fetal brain development and injury mechanisms remain limited. This study introduces a human iPSC-derived myelination model developed using a microfluidic device. The platform combines spinal cord-patterned neuronal and oligodendrocyte spheroids to recapitulate axon-glia interactions and myelination processes . The model successfully achieved axonal fascicle formation and compact myelin deposition, as validated by immunostaining and transmission electron microscopy. Functional calcium imaging confirmed neuronal activity within the system, underscoring its physiological relevance. While myelination efficiency was partial, with some axons remaining unmyelinated under the current conditions, this model represents a significant advancement in human myelin biology, offering a foundation for investigating fetal and perinatal brain injuries and related pathologies. Future refinements, such as improved myelination coverage and incorporating additional CNS cell types, will enhance its utility for studying disease mechanisms and enabling high-throughput drug screening.
脑白质损伤，如脑室周围白质软化，是早产儿神经发育障碍的主要原因。尽管这些病症具有临床意义，但用于研究胎儿脑发育和损伤机制的与人类相关的模型仍然有限。本研究介绍了一种使用微流控装置开发的人诱导多能干细胞衍生的髓鞘形成模型。该平台结合了脊髓模式的神经元和少突胶质细胞球体，以重现轴突-神经胶质相互作用和髓鞘形成过程。通过免疫染色和透射电子显微镜验证，该模型成功实现了轴突束的形成和紧密髓鞘沉积。功能性钙成像证实了系统内的神经元活动，强调了其生理相关性。虽然髓鞘形成效率是部分的，在当前条件下一些轴突仍未髓鞘化，但该模型代表了人类髓鞘生物学的重大进展，为研究胎儿和围产期脑损伤及相关病理提供了基础。未来的改进，如提高髓鞘形成覆盖率和纳入额外的中枢神经系统细胞类型，将增强其用于研究疾病机制和进行高通量药物筛选的效用。
