Engineering transferrable microvascular meshes for subcutaneous islet transplantation

构建可转移微血管网用于皮下胰岛移植

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作者:Wei Song, Alan Chiu, Long-Hai Wang, Robert E Schwartz, Bin Li, Nikolaos Bouklas, Daniel T Bowers, Duo An, Soon Hon Cheong, James A Flanders, Yehudah Pardo, Qingsheng Liu, Xi Wang, Vivian K Lee, Guohao Dai, Minglin Ma

Abstract

The success of engineered cell or tissue implants is dependent on vascular regeneration to meet adequate metabolic requirements. However, development of a broadly applicable strategy for stable and functional vascularization has remained challenging. We report here highly organized and resilient microvascular meshes fabricated through a controllable anchored self-assembly method. The microvascular meshes are scalable to centimeters, almost free of defects and transferrable to diverse substrates, ready for transplantation. They promote formation of functional blood vessels, with a density as high as ~220 vessels mm-2, in the poorly vascularized subcutaneous space of SCID-Beige mice. We further demonstrate the feasibility of fabricating microvascular meshes from human induced pluripotent stem cell-derived endothelial cells, opening a way to engineer patient-specific microvasculature. As a proof-of-concept for type 1 diabetes treatment, we combine microvascular meshes and subcutaneously transplanted rat islets and achieve correction of chemically induced diabetes in SCID-Beige mice for 3 months.

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