Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy

Diabetic patients undergoing hyperbaric oxygen therapies (HBO2T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO2T CD34(+) cell population contains two-to threefold higher levels of hypoxia inducible factors-1, -2, and -3, as well as thioredoxin-1 (p < 0.003), than cells present in blood before HBO2T. Skin margins obtained from 2-day-old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor-1, and Trx-1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO2T (p < 0.003). HBO2T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO2T and remains elevated for at least 20 hours. We conclude that HBO2T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.