Stable intracranial imaging of dura mater-engrafted pancreatic islet cells in awake mice

Philip Tröster (), Montse Visa, Ismael Valladolid-Acebes, Martin Köhler and Per-Olof Berggren
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Philip Tröster: Karolinska Institutet
Montse Visa: Karolinska Institutet
Ismael Valladolid-Acebes: Karolinska Institutet
Martin Köhler: Karolinska Institutet
Per-Olof Berggren: Karolinska Institutet

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract By transplanting pancreatic islets onto the dura mater of the mouse brain, we establish a microscopy platform that enables longitudinal intravital imaging of otherwise optically inaccessible tissue. The system combines a cranial window with an air-cushioned floating arena and stable head fixation, providing high mechanical stability for repeated single-cell Ca2+ imaging sessions of up to 90 min in awake mice. We show that dura mater-engrafted islets integrate with host vascular and neural networks, and that human islet grafts secrete C-peptide in response to glucose stimulation, indicating metabolic integration. With this platform, we monitor anesthesia-induced changes in capillary blood flow and islet Ca2+ dynamics. In awake mice, following subcutaneous glucose injection, we characterize intracellular Ca2+ oscillations in insulin-secreting β-cells, revealing changes in amplitude, period, and plateau fraction while network coordination remains stable. The dura mater thus offers long-term optical access to functional endocrine tissue, facilitating stable intravital imaging under anesthesia-free, physiological conditions.

Date: 2025
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DOI: 10.1038/s41467-025-66057-4

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