Engineering transferrable microvascular meshes for subcutaneous islet transplantation

• Published in: Nature communications Vol. 10; no. 1; pp. 4602 - 12
• Main Authors: Song, Wei, Chiu, Alan, Wang, Long-Hai, Schwartz, Robert E., Li, Bin, Bouklas, Nikolaos, Bowers, Daniel T., An, Duo, Cheong, Soon Hon, Flanders, James A., Pardo, Yehudah, Liu, Qingsheng, Wang, Xi, Lee, Vivian K., Dai, Guohao, Ma, Minglin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-10-2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/107; 13/51; 14/63; 142/126; 147/135; 631/61/2035; 692/699/2743/137/1418; Animals; Bioengineering; Blood vessels; Cell Culture Techniques - instrumentation; Cell Culture Techniques - methods; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - therapy; Endothelial cells; Female; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Hyperglycemia - therapy; Implants; Induced Pluripotent Stem Cells - cytology; Islet cells; Islets of Langerhans Transplantation - instrumentation; Islets of Langerhans Transplantation - methods; Male; Mice; Mice, SCID; Microvasculature; Microvessels - cytology; Microvessels - growth & development; Microvessels - physiology; multidisciplinary; Neovascularization, Physiologic; Organic chemistry; Pancreatic islet transplantation; Pluripotency; Rats, Sprague-Dawley; Regeneration; Science; Science (multidisciplinary); Self-assembly; Stem cells; Substrates; Transplantation; Transplants & implants; Vascularization
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12373-5

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.
The success of engineered tissue depends on the integration of a dense vascular network to supply nutrients and remove waste products. Here the authors design high density microvascular meshes made through an anchored self-assembly mechanism, and use these meshes to support subcutaneous pancreatic islet survival in a mouse diabetes model.