Post-transplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: a promising clinical alternative to the conventional intrahepatic site

5 years ago

Post-transplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: a promising clinical alternative to the conventional intrahepatic site

N. Gonzalez, K. Omori, J. Li, Y. Mullen, D. Mendez, F. Kandeel, J. Rawson, H. Komatsu, A. Barriga

Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose-bFGF. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mmHg, compared to 45 mmHg under ambient air. In vitro, islets cultured under 140 mmHg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mmHg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with post-operative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14497