Key Takeaways & Executive Findings
- •• Intracerebral transplantation of autologous mesenchymal stromal cells (MSC) in subacute ischemic stroke patients led to significant increases in FDG-PET and IMZ-SPECT uptake in peri-infarct cortical regions, indicating improved glucose metabolism and synaptic density/viability. • The observed improvements in brain imaging biomarkers were strongly correlated with functional recovery, suggesting that MSC transplantation may enhance neuronal integrity and promote neurological rehabilitation. • This study provides the first serial imaging evidence in humans that cell therapy can modulate host brain metabolism and receptor binding potential, supporting the translational potential of MSC-based regenerative medicine for stroke. • The findings highlight the importance of multimodal neuroimaging (FDG-PET and IMZ-SPECT) in monitoring therapeutic responses and guiding patient selection for cell-based interventions in stroke.
Abstract
Ischemic stroke is a leading cause of mortality and long-term neurological disability worldwide, and cell-based therapies represent a promising approach. Although clinical studies have reported favorable outcomes following cell transplantation, the effects on host neuronal integrity remain incompletely understood. This study investigated temporal and spatial changes in fluorodeoxyglucose positron emission tomography (FDG-PET) and 123I-iomazenil single-photon emission computed tomography (IMZ-SPECT) after intracerebral cell transplantation in patients with subacute ischemic stroke and examined their relationship with functional recovery. Seven adults with severe post-stroke disability underwent autologous mesenchymal stromal cell (HUNS001-01) transplantation 47–64 days after stroke onset. Brain FDG-PET and IMZ-SPECT were performed preoperatively and at 1, 3, and 12 months post-transplantation. Regions of interest were first manually set in the ipsilateral cortex where the 12-month postoperative-to-preoperative standard uptake value ratio seems increased, and followed by quantitative measurement. Five of seven patients demonstrated 5% or more increase of FDG-PET and/or IMZ-SPECT uptake in peri-infarct cortical regions, predominantly within the frontal or temporal cortex. Transplanted cells localized either within metabolically enhanced regions or in anatomically remote areas. FDG-PET and IMZ-SPECT changes were strongly interacted in each other and were associated with functional improvement. Overall, improvement of glucose metabolism and synaptic density/viability were observed in patient with subacute ischemic stroke, which may have been attributable to cell transplantation. Trial registration: UMIN000026130.
1. Introduction
Ischemic stroke remains one of the leading causes of death and disability globally. Currently, the only approved treatments are intravenous recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy, with no effective therapeutic options available after the subacute phase of the disease [1]. In this context, cell therapy emerges as a promising strategy to enhance functional recovery in patients suffering from subacute or chronic ischemic stroke, with numerous clinical trials demonstrating favorable results [2].
Regarding the mode of action, preclinical studies have highlighted the potential roles of transplanted cells, including cell differentiation to neural lineage, anti-inflammatory effects, and the stimulation of endogenous repair mechanisms through paracrine effect [3–5]. These findings have been corroborated by improvements in brain glucose metabolism and neural receptor binding potential at the peri-infarct area in the host animal brain [6–9]. However, alterations of these neuronal integrities following cell transplantation have yet to be fully elucidated in the human subjects.
Our group previously reported that intracerebral transplantation of autologous mesenchymal stromal cells (MSC; HUNS001-01) successfully facilitated neurological recovery in a patient with subacute ischemic stroke [10]. This study also employed serial fluorodeoxyglucose positron emission tomography (FDG-PET) and 123I-Iomazenil single-photon emission computed tomography (IMZ-SPECT) imaging to clarify brain glucose metabolism and synaptic receptor binding potential, respectively. Thus, the current analysis aims to evaluate the temporo-spatial changes of glucose metabolism and synaptic density/viability in relation to functional recovery in patients who participated in this clinical trial.
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Masahito Kawabori, Kenji Hirata, Hideo Shichinohe, Shiro Watanabe, Arisa Miura, Yoichi M. Ito, Kohsuke Kudo, Satoshi Kuroda, Kiyohiro Houkin, Miki Fujimura (2026). Serial brain FDG-PET and IMZ-SPECT following intracerebral MSC transplantation in patients with subacute ischemic stroke. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-026-05048-8
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Frequently Asked Questions
What is the main finding of this study?
The study found that intracerebral transplantation of autologous mesenchymal stromal cells in patients with subacute ischemic stroke led to significant increases in FDG-PET and IMZ-SPECT uptake in peri-infarct cortical regions, indicating improved glucose metabolism and synaptic density/viability, which were associated with functional recovery.
How many patients were included in the study?
Seven adults with severe post-stroke disability were included in the study.
What imaging techniques were used?
The study used fluorodeoxyglucose positron emission tomography (FDG-PET) and 123I-iomazenil single-photon emission computed tomography (IMZ-SPECT) to assess brain glucose metabolism and synaptic receptor binding potential, respectively.
What is the significance of this research?
This research provides the first serial imaging evidence in humans that cell therapy can modulate host brain metabolism and receptor binding potential, supporting the translational potential of MSC-based regenerative medicine for stroke.
What is the trial registration number?
The trial registration number is UMIN000026130.
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