title: Engineered blood vessel networks connect to host vasculature via wrapping-and-tapping anastomosis.
abstract: Rapid blood perfusion is critical for postimplantation survival of thick, prevascularized bioartificial tissues. Yet the mechanism by which implanted vascular networks inosculate, or anastomose, with the host vasculature has been unknown, making it difficult to develop optimized strategies for facilitating perfusion. Here we show that implanted vascular networks anastomose with host vessels through a previously unidentified process of "wrapping and tapping" between the engrafted endothelial cells (ECs) and the host vasculature. At the host-implant interface, implanted ECs first wrap around nearby host vessels and then cause basement membrane and pericyte reorganization and localized displacement of the underlying host endothelium. In this way, the implanted ECs replace segments of host vessels to divert blood flow to the developing implanted vascular network. The process is facilitated by high levels of matrix metalloproteinase-14 and matrix metalloproteinase-9 expressed by the wrapping ECs. These findings open the door to new strategies for improving perfusion of tissue grafts and may have implications for other physiologic and pathologic processes involving postnatal vasculogenesis.
authors.affiliation: Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Shan
authors.initials: S
authors.lastname: Liao
authors.forename: Hon
authors.initials: H
authors.lastname: Kit Wong
authors.forename: Delphine A
authors.initials: DA
authors.lastname: Lacorre
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: di Tomaso
authors.forename: Patrick
authors.initials: P
authors.lastname: Au
authors.forename: Dai
authors.initials: D
authors.lastname: Fukumura
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: Lance L
authors.initials: LL
authors.lastname: Munn
mesh_terms: D000818:Animals; D001163:Arteriovenous Anastomosis / Q000502:physiology*; D001807:Blood Vessel Prosthesis; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D006085:Graft Survival / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D055806:Microvessels / Q000166:cytology / Q000502:physiology*; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000502:physiology; D020286:Pericytes / Q000166:cytology / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods