title: Increased numbers of low-oxygenated pancreatic islets after intraportal islet transplantation.
abstract: OBJECTIVE
  No previous study has measured the oxygenation of intraportally transplanted islets, although recent data suggest that insufficient engraftment may result in hypoxia and loss of islet cells.
  
  
  METHODS
  After intraportal infusion into syngeneic mice, islet oxygenation was investigated in 1-day-old, 1-month-old, or 3-month-old grafts and compared with renal subcapsular grafts and native islets. Animals received an intravenous injection of pimonidazole for immunohistochemical detection of low-oxygenated islet cells (pO(2) <10 mmHg), and caspase-3 immunostaining was performed to assess apoptosis rates in adjacent tissue sections.
  
  
  RESULTS
  In the native pancreas of nontransplanted animals, ∼30% of the islets stained positive for pimonidazole. In 1-day-old and 1-month-old grafts, the percentage of pimonidazole-positive islets in the liver was twice that of native islets, whereas this increase was abolished in 3-month-old grafts. Beneath the renal capsule, pimonidazole accumulation was, however, similar to native islets at all time points. Apoptosis rates were markedly increased in 1-day-old intrahepatic grafts compared with corresponding renal islet grafts, which were slightly increased compared with native islets. One month posttransplantation renal subcapsular grafts had similar frequencies of apoptosis as native islets, whereas apoptosis in intraportally implanted islets was still high. In the liver, islet graft vascular density increased between 1 and 3 months posttransplantation, and apoptosis rates simultaneously dropped to values similar to those observed in native islets.
  
  
  CONCLUSIONS
  The vascular engraftment of intraportally transplanted islets is markedly delayed compared with renal islet grafts. The prolonged ischemia of intraportally transplanted islets may favor an alternative implantation site.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. richard.olsson@karolinska.se
authors.forename: Richard
authors.initials: R
authors.lastname: Olsson
authors.forename: Johan
authors.initials: J
authors.lastname: Olerud
authors.forename: Ulrika
authors.initials: U
authors.lastname: Pettersson
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D006085:Graft Survival; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009593:Nitroimidazoles / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
chemical_list: D007328:Insulin; D009593:Nitroimidazoles; C033815:pimonidazole; D053148:Caspase 3; D010100:Oxygen