Hyperbaric oxygen therapy improves early posttransplant islet function

Authors

  • Naoaki Sakata,

    1. Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
    2. Division of Hepato-Biliary Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
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  • Nathaniel K Chan,

    1. Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • Robert P Ostrowski,

    1. Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • John Chrisler,

    1. Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • Pete Hayes,

    1. Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • Sonny Kim,

    1. Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • Andre Obenaus,

    1. Department of Radiation Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
    2. Department of Radiology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • John H Zhang,

    1. Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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  • Eba Hathout

    Corresponding author
    1. Department of Pediatrics, Islet Transplant Laboratory, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
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Eba Hathout, MD, Professor and Chief, Division of Pediatric Endocrinology, Director, Department of Pediatrics, Pediatric Diabetes Center and Islet Transplant Laboratory, Loma Linda University School of Medicine, 11175 Campus Street, Coleman Pavilion, A1120R, Loma Linda, CA 92354, USA. Tel: +1 909 558 4773; fax: +1 909 558 0408; e-mail: ehathout@llu.edu

Abstract

Sakata N, Chan NK, Ostrowski RP, Chrisler J, Hayes P, Kim S, Obenaus A, Zhang JH, Hathout E. 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.

Conclusion: 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.

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