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A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo

免疫系统 体内 移植 小岛 细胞生物学 生物 免疫学 医学 内科学 糖尿病 内分泌学 生物技术
作者
Siddharth Krishnan,Claudia Liu,Matthew A. Bochenek,Sugata Bose,Nader El Khatib,Benjamin Walters,Lucy M. O’Keeffe,Amanda Facklam,Robert Langer,Daniel G. Anderson
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [National Academy of Sciences]
卷期号:120 (40)
标识
DOI:10.1073/pnas.2311707120
摘要

The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals.
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