The Role of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Treatment of Stroke

Abstract

Stroke is a serious cerebrovascular disease that causes high mortality and persistent disability in adults worldwide. Stroke is also an enormous public health problem and a heavy public financial burden in the United States. Treatment for stroke is very limited. Thrombolytic therapy by tissue plasminogen activator (tPA) is the only approved treatment for acute stroke, and no effective treatment is available for chronic stroke. Developing new therapeutic strategies, therefore, is a critical need for stroke treatment. This article summarizes the discovery of new routes of treatment for acute and chronic stroke using two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF). In a study of acute stroke, SCF and G-CSF alone or in combination displays neuroprotective effects in an animal model of stroke. SCF appears to be the optimal treatment for acute stroke as the functional outcome is superior to G-CSF alone or in combination (SCF+G-CSF); however, SCF+G-CSF does show better functional recovery than G-CSF. In a chronic stroke study, the therapeutic effects of SCF and G-CSF alone or in combination appear differently as compared with their effects on the acute stroke. SCF+G-CSF induces stable and long-lasting functional improvement; SCF alone also improves functional outcome but its effectiveness is less than SCF+G-CSF, whereas G-CSF shows no therapeutic effects. Although the mechanism by which SCF+G-CSF repairs the brain in chronic stroke remains poorly understood, our recent findings suggest that the SCF+G-CSF-induced functional improvement in chronic stroke is associated with a contribution to increasing angiogenesis and neurogenesis through bone marrow-derived cells and the direct effects on stimulating neurons to form new neuronal networks. These findings would assist in developing new treatment for stroke. The article presents some promising patents on role of stem cell factor and granulocyte-colony stimulating factor in treatment of stroke.