Intravital Multimodal Imaging of Human Cortical Organoid Transplantation in a Mouse Model of Chronic Stroke.

Overview

1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
2. Department of Electrical and Computer Engineering, Princeton University, Princeton, NJ, USA
3. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
4. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, USA
5. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
6. Omenn Darling Bioengineering Institute, Princeton University, Princeton, NJ, USA

Abstract

Chronic stroke poses enduring neurological deficits, while experimental strategies based on human induced pluripotent stem cell‐derived cortical organoids (COs) remain limited by the lack of tools for longitudinal in vivo graft monitoring. Here, we introduce the Multimodal Imaging Platform for Organoid Tracking (MIPOT), integrating MRI, bioluminescence imaging, surgical microscopy, and intravital two‐photon fluorescence microscopy to monitor CO transplantation in chronic stroke lesions in mice. MIPOT enabled confirmation of initial graft placement within cleaned infarct cavities, longitudinal assessment of viability‐associated bioluminescence signals, and high‐resolution visualization of graft‐derived cells and short‐term cellular dynamics. Bioluminescence imaging revealed a progressive decline in graft‐associated signals that stabilized at approximately 25% by two weeks, while endpoint histology confirmed limited persistence of human graft‐derived cells at later time points. Together, MIPOT provides a multimodal framework for monitoring organoid transplantation in the injured brain and supports future optimization of graft survival, maturation, and host–graft integration.

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Data Availability Statement

Design files for the removable 3D‐printed head‐fixation system and data analysis are available at https://github.com/liangy10/MIPOT. All data are available from the Lead Contact, Yajie Liang (), upon request.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 5 keywords, 10 MeSH terms, 7 funders, 68 references, 1 RRID.

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This paper

Wang, J., Qiao, G., Tan, H., Russel, C., Yang, B., Li, M. J., Wang, K., Xu, J., Chu, C., Janowski, M., Fu, T., Walczak, P., & Liang, Y. (2026). Intravital Multimodal Imaging of Human Cortical Organoid Transplantation in a Mouse Model of Chronic Stroke. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(52), e15913. https://doi.org/10.1002/advs.202515913

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