Intermittent normobaric oxygen inhalation enhances subcutaneous prevascularization for cell transplantation.

PURPOSE

Subcutaneous tissue is a promising site for cell transplantation; advantages include minimally invasive procedures and easy post-transplant monitoring. However, limited vascularity is the major known challenge. To address this challenge, a prevascularized graft bed is prepared in recipients. We aimed to establish an improved, clinically applicable approach to promote prevascularization of the subcutaneous graft bed prior to cell transplantation.

METHODS

We applied a conventional prevascularization approach by subcutaneously implanting nylon discs into the backs of Lewis rats. After disc implantation, we treated rats with or without intermittent normobaric 100% oxygen inhalation (1 h, twice a day, for consecutive 7 days). We used histology to compare vascular density between the oxygen-treated or control groups. To assess the functional effects of prevascularization, we transplanted three hundred islets isolated from luciferase-transgenic Lewis rats into the oxygen-treated or control wild type Lewis recipients, then used bioluminescence imaging to track engraftment for 4 weeks.

RESULTS

Oxygen treatment significantly augmented prevascularization in the subcutaneous site compared to controls. Islet transplantation into prevascularized graft beds demonstrated significant improvement in engraftment efficiency in oxygen-treated recipients compared to controls at 2-4 weeks post-transplantation.

CONCLUSION

Combining intermittent normobaric 100% oxygen inhalation with a conventional vascularization approach promotes a functional vasculature within a week. A simple approach using normobaric oxygen has the potential for translation into clinical application in subcutaneous site cell transplantations.