Hyperbaric oxygen therapy improves early posttransplant islet function.
OBJECTIVE
This study investigates the therapeutic potential of hyperbaric oxygen therapy (HBO) in reducing hypoxia and improving engraftment of intraportal islet transplants by promoting angiogenesis.


METHODS
Diabetic BALB/c mice were transplanted with 500 syngeneic islets intraportally and received six consecutive twice-daily HBO treatments (n = 9; 100% oxygen for 1 h at 2.5 atmospheres absolute) after transplantation. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) was used to assess new vessel formation at postoperative days (POD) 3, 7, and 14. Liver tissue was recovered at the same time points for correlative histology, including: hematoxylin and eosin, hypoxia-inducible factor (HIF1α), Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), vascular endothelial growth factor (VEGF), and von Willebrand Factor immunohistochemistry.


RESULTS
HBO therapy significantly reduced HIF-1α, TUNEL and VEGF expression in islets at POD 7. In the non-HBO transplants, liver enhancement on DCE MRI peaked at POD 7 consistent with less mature vasculature but this enhancement was suppressed at POD 7 in the HBO-treated group. The number of new peri-islet vessels at POD 7 was not significantly different between HBO and control groups.


CONCLUSIONS
These results are consistent with a hyperbaric oxygen-mediated decrease in hypoxia that appeared to enhance vessel maturation in the critical days following intraportal islet transplantation.
Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
Naoaki
N
Sakata
Nathaniel K
NK
Chan
Robert P
RP
Ostrowski
John
J
Chrisler
Pete
P
Hayes
Sonny
S
Kim
Andre
A
Obenaus
John H
JH
Zhang
Eba
E
Hathout
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D006931:Hyperbaric Oxygenation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007515:Islets of Langerhans / Q000098:blood supply / Q000502:physiology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A