The neuroprotective effect of erythropoietin-transduced human mesenchymal stromal cells in an animal model of ischemic stroke

Toward a More Effective Intravascular Cell Therapy in Stroke

“…Human BM-MSCs have also been genetically modified to express neuroprotective/ angiogenic growth factors, such as brain derived neurotrophic factor (BDNF) (Kurozumi et al, 2004;Nomura et al, 2005), placental growth factor (PlGF) (Liu et al, 2006), glial cell linederived neurotrophic factor (GDNF) (Horita et al, 2006), erythropoietin (Cho et al, 2010), and vascular endothelial growth factor (VEGF) combined with angiopoietin-1 (Toyama et al, 2009). All these modified MSCs have shown their ability to improve functional recovery in ischemic rats, compared to unmodified MSCs, when delivered intravenously.…”

The Promise of Hematopoietic Stem Cell Therapy for Stroke: Are We There Yet?

“…For example, erythropoietin (EPO) is a known antioxidant, anti-apoptotic and anti-inflammatory (Chong et al, 2003). However, EPO cannot cross the blood barrier if injected IV and therefore its beneficial effect on the brain cannot be evaluated (Cho et al, 2010). Cho et al transduced BMSC to produce increased levels of EPO, and sterotaxically implanted 6x10 5 cells.…”

“…The transduced cells were shown to secrete higher levels of BDNF, SDF1-A and TGF1-b. Animals which received the transduced BMSC had improved neurological function, lower infarct volumes and higher levels of phosphorylated AKT (a downstream effector of EPO) (Cho et al, 2010).…”

“…Actual HSC numbers needed for adminitration in stroke patients for receovery is critical for those considering an autologus transplantation from their own bone marrow. The route of injection of HSC also varied from IV Leonardo et al, 2010;Regelsberger et al, 2011), to IA (Keimpema et al, 2009) and direct implantation in the brain (Cho et al, 2010). Maikinen et al (2006) showed that IV injection of HSC lead to them being trapped in the spleen and kidneys and none of the cells were detected in the brain following the stroke.…”

Evaluation of parametric response mapping to assess therapeutic response to human mesenchymal stem cells after experimental stroke

“…7 Although the underlying mechanisms by which transplanted hMSCs ameliorate stroke prognosis are still poorly understood, reduction in immune cell infiltration and demyelination, the secretion of growth and/or trophic factors, and the promotion of angiogenesis could be primarily responsible. [7][8][9] Enhancement of the differentiation of stem cells into the original cell lineages of the damaged tissue or selective migration of cells to ischemic regions to support plasticity may eventually improve functional recovery after ischemia. 10,11 Moreover, among all the administration routes available (intracerebral, intrathecal, intraarterial, and intravenous [IV]), the less invasive IV administration appears today safer and easier than the local brain grafting following stroke in the clinical setting and allows cell distribution into vascularized and viable areas of the lesion.…”