Intravital Multimodal Imaging of Human Cortical Organoids for Chronic Stroke Treatment in Mice
Year: 2025
Type: preprint
Abstract: Chronic stroke leads to enduring neurological deficits and remains a major clinical challenge. Human induced pluripotent stem cell (hiPSC)-derived cortical organoids (COs) offer promise for regenerative therapies, yet their application in chronic stroke remains understudied, in part due to limited tools for monitoring graft in vivo. Here, we present a Multimodal Imaging Platform for Organoid Tracking (MIPOT), which integrates MRI, bioluminescence imaging, light microscopy, and two-photon fluorescence microscopy to noninvasively track transplanted COs in the post-stroke brain over time. Using MIPOT, we verified precise delivery of COs into cleaned stroke cavities, observed progressive declines in viability within the first 10 days, and introduced labeling methods for functional in vivo tracking of COs at subcellular resolution. By 4 weeks post-transplantation, histological analysis revealed survival of COs in the cerebral cortex. Notably, COs engrafted into the hippocampus displayed enhanced maturation, underscoring the role of local microenvironments in graft integration. MIPOT enables dynamic, noninvasive evaluation of hiPSC COs in chronic stroke, providing a foundation for mechanistic studies and translational development of organoid-based therapies.
Authors: Jinghui Wang, Guanda Qiao, Honglin Tan, Mengyang Jacky Li, Kexin Wang, Jiadi Xu, Miroslaw Janowski, Tian-Ming Fu, Piotr Walczak, Yajie Liang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Metasurface-Integrated Open-Top Lattice Light Sheet Microscope for High-Throughput Bioimaging, Shedding light on functional heterogeneity of dementia-related alpha-synuclein strains, Intravital 2-photon imaging the integration of transplanted embryonic neurons in a mouse model of cerebral ischemia at the subacute phase, Intravital 2-photon microscopy enabling 6D single cell RNA seq in immunocompetent glioblastoma xenografts, Altered pH in early Alzheimer's disease detected by creatine chemical exchange saturation transfer MRI, Image-guided intra-arterial administration of antibody-releasing glial progenitors to control the HIV CNS reservoir., G900841757
OpenAlex ID: W4412065852