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

TL;DR

This study introduces a new method to image pancreatic islet cells in awake mice by transplanting them onto the brain's dura mater, enabling long-term observation of their function.

Contribution

The novel approach uses the dura mater as a site for islet transplantation, allowing stable intravital imaging in awake mice without anesthesia.

Findings

Dura mater-engrafted islets integrate with host vascular and neural networks.

Human islet grafts secrete C-peptide in response to glucose, showing metabolic integration.

Intracellular Ca2+ oscillations in β-cells reveal changes in amplitude and period under physiological conditions.

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.

Imaging pancreatic islets in living animals is often limited by poor optical access and motion instability. Here, the authors show that transplanting islets onto the brain’s dura mater enables stable, long-term, and functional imaging in awake mice.

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