Engineering transferrable microvascular meshes for subcutaneous islet transplantation

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 and Minglin Ma ()
Additional contact information
Wei Song: Cornell University
Alan Chiu: Cornell University
Long-Hai Wang: Cornell University
Robert E. Schwartz: Weill Cornell Medical College
Bin Li: Cornell University
Nikolaos Bouklas: Cornell University
Daniel T. Bowers: Cornell University
Duo An: Cornell University
Soon Hon Cheong: Cornell University
James A. Flanders: Cornell University
Yehudah Pardo: Cornell University
Qingsheng Liu: Cornell University
Xi Wang: Cornell University
Vivian K. Lee: Northeastern University
Guohao Dai: Northeastern University
Minglin Ma: Cornell University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12373-5

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