Embryonic Stem Cell-Derived Multipotent Mesenchymal Stromal Cell Therapy Following Focal Ischemia in the Rat

摘要: Stroke is a major public health concern, with ~795,000 strokes occurring in the United States each year, resulting over 130,000 deaths annually, and 4.8 million stroke survivors (CDC Risk Survey 2008). The estimated direct indirect cost of for 2010 $73.7 billion Clinical treatment options ischemic (which accounts ~87% cases) are limited to chemical or mechanical clot-busting interventions during short time-window following stroke. Therefore, development post-ischemic therapies reduce mortality disability associated would have clear benefits. Multipotent mesenchymal stromal cell (MSC; also sometimes called stem cell) transplantation has shown protection against animal models, reducing infarct volumes improving behavioral function (Chen et al. 2001; Li 2001); transplanted MSCs, however, often do not show long-term survival integration into brain. This led many investigators believe that paracrine mechanisms underlie benefits MSC transplantation. Indeed, neural derivatives, such as neuroepithelial cells, may be better suited than MSCs promote neuronal replacement due their neuroectodermal developmental origin (Kelly 2004; Jiang 2006; Darsalia 2007; Fong Daadi Transplanted cells face hostile, inflammatory environment near term cerebrum, which contribute engrafted cells. induces gene expression changes suggest an altered response ischemia (Ohtaki In addition promotion endogenous repair processes, this modulation (Aggarwal & Pittenger 2005) provide ameliorated prosurvival and/or pro-differentiation milieu subsequent other types, Addressing issues potential allograft rejection survival/replacement will important clinical application therapies, regardless type used. immunosuppressive attributes put them under consideration use co-transplantation approaches mitigate graft concerns.