In 2003, we started a phase I/IIa clinical trial regarding the intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34+ cells in 17 patients with critical limb ischemia (CLI). No major amputation occurred and the CLI-free ratio was as high as 88%, one year post cell therapy. Ulcer area, toe brachial pressure index, and walking distance significantly improved after the treatment. We confirmed the long-term efficacy and safety of this cell therapy up to 4 years. From 2008, we performed the first investigator-led clinical trial under good clinical practice in the field of regenerative medicine in Japan. Favorable outcomes in terms of safety and efficacy were reproduced in this phase II trial. We are now preparing for the phase III, pivotal trial for pharmaceutical approval of the cell-based vascular regeneration therapy.
It has been proposed that abnormalities in physical properties of the cell membranes may strongly be linked to hypertension and other circulatory disorders. Recent studies have shown that adipokines might actively participate in the pathophysiology of hypertension and in the metabolic syndrome. The purpose of the present article is to elucidate the possible relationships among adipokines, endothelial function, and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The ESR study demonstrated that membrane fluidity was significantly decreased in hypertensive subjects compared to normotensive subjects. The reduced membrane fluidity of RBCs was associated with decreased levels of plasma nitric oxide (NO)-metabolites and increased levels of plasma asymmetric dimethylarginine (ADMA; an endogenous NO synthase inhibitor), indicating that endothelial function could be a determinant of membrane fluidity of RBCs. Leptin, an adipokine, significantly increased membrane fluidity of RBCs, at least in part, via the NO-dependent mechanism. Furthermore, higher levels of plasma adiponectin were associated with increased membrane fluidity of RBCs. On the other hand, intervention with hormone (estrogen) replacement therapy or administration of benidipine, a Ca channel blocker, significantly improved membrane fluidity of RBCs with a concomitant increase in plasma NO metabolite levels. In this context, it is strongly suggested that both NO and adipokines might have a crucial role in the regulation of rheologic behavior of RBCs and microcirculation in hypertension.
Young healthy people sometimes suffer from Paget-Schroetter syndrome, which is a relatively rare condition that has been associated with a controversial treatment strategy. This case report presents a male patient in his 40’s, who visited our hospital because of sudden swelling of the right arm. Thrombosis of the right subclavian vein was detected by ultrasound and enhanced computed tomography. Transcatheter thrombectomy and thrombolysis were performed. The patient was diagnosed with Paget-Schroetter syndrome and, subsequently, underwent surgery. Using a subclavicular approach, the first right rib, costoclavicular ligament, and anterior scalene muscles were resected, and intraoperative venography revealed stenosis. Subsequently, the manubrium of the sternum was divided into an L-shape incision and a vein patch was performed. The patient showed an excellent postoperative course that required only 8 weeks of anticoagulation treatment. No recurrence was reported 6 months after surgery.