title: Islet engraftment and revascularization in clinical and experimental transplantation.
abstract: Proper revascularization after transplantation is assumed to be crucial for appropriate islet graft function. We developed a novel noninvasive imaging method, based on adenoviral transduction of islets with a hypoxia responsive reporter gene, for continuous in vivo monitoring of hypoxia  in islet grafts in a mouse model. In addition, morphological data were obtained from a deceased patient previously subject to intraportal transplantation. We detected only transient hypoxia in a minority of the animals transplanted. Importantly, a clear response to hypoxia was observed in  vitro after removal of the islet grafts on day 28 after transplantation. Also, the morphological data from the deceased patient demonstrated an extensive revascularization of the transplanted islets. In fact, no differences could be seen between native islets, in pancreas biopsies taken prior  to islet isolation, and transplanted islets regarding the number, distribution, and shape of the blood vessels. However, fewer small islets (diameter <39 µm) were found in the liver compared to those found in native pancreases. Notably, an absolute majority of the transplanted islets  were found remaining within the venous lumen, in direct contact with the vessel wall. In conclusion, the results presented show less pronounced islet graft hypoxia after subcapsular transplantation than previously reported using more invasive methods. Also, formation of an extensive intraislet  capillary network, similar to that seen in native islets in the pancreas, was seen after clinical islet transplantation.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. cgmolnar@yahoo.co.uk
authors.forename: Christian
authors.initials: C
authors.lastname: Molnár
authors.forename: Magnus
authors.initials: M
authors.lastname: Essand
authors.forename: Lars
authors.initials: L
authors.lastname: Wennberg
authors.forename: Christian
authors.initials: C
authors.lastname: Berne
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tufveson
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007515:Islets of Langerhans / Q000098:blood supply* / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology