Abstract 11150: Hyperbaric Oxygenation Enhances Transplanted Cell Graft Survival and Functional Recovery in Critical Limb Ischemia

Abstract

Introduction: One of the major limitations in the application of stem-cell therapy to repair ischemic tissue is the low survival of transplanted cells, possibly due to poor oxygenation. Also the effect of hyperbaric oxygen therapy (HBOT) on bone marrow-derived mesenchymal stem cells (MSCs) is poorly understood. Hypothesis: We hypothesized that HBOT could be used as an adjuvant treatment to augment stem-cell therapy. Therefore, this study aimed to evaluate the effect of HBOT on the engraftment of bone marrow-derived MSCs transplanted in critical limb ischemia (CLI). Methods: Sixty-nine consecutive CLI patients refractory to peripheral revascularization therapy were enrolled. MSC transplantation was performed in all patients. HBOT (given 100% oxygen under 2.8 atmosphere absolute, for 60 min) was administered to 36 patients with and 33 patients without, by 2 weeks after those therapies. These patients were followed up by an outpatient clinic after limb survival. The primary endpoint was tissue oxygen tension of blood flow recovery, and secondary endpoint was adverse event rate (death and major limb amputation), analyzed by intention-to-treat. Results: Mean follow up was 11.4 ± 0.6 years. Limb survival rate was 84.1% and survival was 76.8%. The effect of HBOT was independent of background conditions, such as diabetes and hemodialysis (NS, respectively, Breslow-Day analysis). After 4 weeks, recovery of skin oxygen tension was significantly increased in MSC+HBO group compared to that in MSC group (22.7±16.3 to 34.5±21.4 vs 24.4±15.4 to 28.3±19.6, p = 0.045, odds ratio; 0.194). Surprisingly, in diabetic patients, MSC+HBOT group had significantly lower adverse event rate compared to MSC group (2 vs. 10 cases, p = 0.043, log-rank test, figure). Conclusions: HBOT appears to be a potential and clinically viable non-invasive adjuvant treatment for CLI stem-cell therapy.