Therapeutic angiogenesis for cerebrovascular diseases with hematopoietic stem cells

Abstract

We had been shown that circulating hematopoietic stem cells contributes to the maintenance of vasculature in patients with microvascular diseases and local transplantation of hematopoietic stem cell activates angiogenesis in patients with limb ischemia. In experimental stroke model, we had been shown that intravenous administration of bone marrow–derived hematopoietic stem cell after stroke improves neurogenesis and functional recovery through enhancing angiogenesis. Based on these observations, we have started phase 1/2a clinical trial of intravenous autologous bone marrow–derived mononuclear cell transplantation in 10 days after onset of stroke for patients with cardiogenic cerebral embolism. Our results indicated that autologous bone marrow–derived mononuclear cell transplantation is feasible and safe even in patients with severe stroke, and patients with cell transplantation have significant better neurological outcomes, compared with historical control. These findings indicated that activation of angiogenesis by hematopoietic stem cell transplantation at sub–acute period after stroke can contribute to improvement of functional recovery, as well as the immunomodulation of inflammation by mesenchymal stem cell transplantation at acute period and activation of remodeling by neuronal stem cell transplantation at chronic period.