Engineering transferrable microvascular meshes for subcutaneous islet transplantation

Nat Commun. 2019 Oct 10;10(1):4602. doi: 10.1038/s41467-019-12373-5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bioengineering
  • Cell Culture Techniques / instrumentation*
  • Cell Culture Techniques / methods
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / therapy*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperglycemia / therapy
  • Induced Pluripotent Stem Cells / cytology
  • Islets of Langerhans Transplantation / instrumentation
  • Islets of Langerhans Transplantation / methods*
  • Male
  • Mice, SCID
  • Microvessels / cytology
  • Microvessels / growth & development*
  • Microvessels / physiology
  • Neovascularization, Physiologic
  • Rats, Sprague-Dawley