Regenerative Medicine for Cerebral Infarction

Abstract

Tissue plasminogen activator (t-PA) is the gold standard drug for cerebral infarction in the acute phase (Adams et al., 2007), but it cannot be administered to all cerebral infarction patients. Some patients who survive the acute phase of cerebral infarction suffer from permanent hemiparesis in the chronic phase, which highlights the need for regenerative medicine to play a more important role in treating such individuals. There are two primary approaches to the use of regenerative medicine for patients with cerebral infarction: exogenous stem cell therapies, and enhancement of endogenous stem cells. Stem cell transplantation is one of the most widely employed strategies using exogenous stem cells. Many studies with experimental animals have shown that stem cell transplantation enhances functional recovery after cerebral infarction (Kameda et al., 2007; Takahashi et al., 2008). Based on the results of animal experiments, several clinical trials for patients with cerebral infarction are currently ongoing, using stem cell transplantation techniques, typically with mesenchymal stem cells (Detante et al.). However, these clinical trials have been started despite a lack of results showing that transplanted stem cells can reliably replace infarct areas. The principal purpose of cell transplantation in these cases is cell replacement, or replacement and restoration of infarct areas. Nevertheless, only a few percent of the transplanted cells typically survive during the chronic phase of cerebral infarction (Lindvall & Kokaia, 2006). Even more problematic is the fact that few of these transplanted stem cells differentiate into neurons with immunohistological and electrophysiological properties (Anderova et al., 2006). Based on these reports, some scientists maintain that functional improvements can be achieved without cell-replacement, that the effects of trophic factors secreted by the transplanted cells are sufficient (Cabrer et al., 2010; Shimada & Spees, 2011). Another approach that regenerative medicine can take is enhancement of endogenous stem cells, based on methods that are less invasive than the use of exogenous stem cells. Deep brain stimulation (DBS) for Parkinson’s disease patients is an example of a standard therapy now used in clinical situations. A previous report using animal subjects has shown that DBS can enhance the neurogenesis of endogenous stem cells (Toda et al., 2008). Based on this report, we evaluated the effectiveness of electrical stimulation on animals with cerebral infarction. Recently, we showed that electrical stimulation of the cerebral cortex during the acute phase of cerebral infarction exerted anti-apoptotic, angiogenic and anti-inflammatory effects through the PI3K-Akt signaling pathway (Baba et al., 2009). Moreover, we showed