Cell Therapy and Structural Plasticity Following Cerebral Ischemia
Conventional therapeutic strategies in stroke, both ischemic and hemorrhagic, have focused on the prevention of further stroke. Stem cell transplantation shifts the paradigm of stroke therapy in that it aims to repair the ischemic brain by facilitating th
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Cell Therapy and Structural Plasticity Following Cerebral Ischemia Stanley Hoang, Henry Jung, Tonya Bliss, and Gary Steinberg
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Introduction
Stroke is one of the leading causes of adult disability in the world. For ischemic stroke, the main therapy is the clot lytic agent tissue plasminogen activator, which must be administered within the first 4.5 h (Del Zoppo et al. 2009). As this time frame is limited and depends on the acute detection of clinical symptoms, much research has focused on preventing secondary injury after an initial ischemic or thrombotic event, although clinical translation has been limited (Ginsberg 2008). A new paradigm shift in therapeutic targets for stroke focuses on brain repair, particularly the brain’s plasticity—the ability to regenerate synaptic structures and reorganize its functional architecture after injury. This phenomenon is observed in many stroke patients who often initially present with acute loss of motor function but then regain a remarkable degree of functional independence in the weeks or months following the insult. Experimental studies have shown that the surrounding uninjured parenchyma generates new dendrites and axons that can, to some extent, compensate for the functional loss of injured tissue. Since brain plasticity occurs days to months after stroke, therapies that target such brain repair would significantly open the therapeutic time window of intervention, thus benefiting a significantly larger patient population than current strategies. Growing evidence points to the potential of cell transplantation therapy to promote
Stanley Hoang and Henry Jung contributed equally to this work S. Hoang, M.D. • H. Jung, M.D. • T. Bliss, Ph.D. • G. Steinberg, M.D., Ph.D. (*) Department of Neurosurgery, Stanford Stroke Center and Stanford Institute for Neuro-Innovation and Translational Neuroscience, Stanford University School of Medicine, 300 Pasteur Drive R281, Stanford, CA 94305-5327, USA e-mail: [email protected]
J. Jolkkonen, P. Walczak (eds.), Cell-Based Therapies in Stroke, DOI 10.1007/978-3-7091-1175-8_1, © Springer-Verlag Wien 2013
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brain plasticity after stroke as will be discussed in this chapter. An assortment of cell types, including brain-, bone marrow-, blood-, and dental pulp-derived progenitors, enhance recovery in experimental models of stroke (Chen et al. 2001a; Darsalia et al. 2011; Guzman et al. 2008a; Hicks et al. 2009; Kelly et al. 2004), reviewed in Bliss et al. (2007), and hemorrhagic stroke (reviewed in Andres et al. 2008b). Due to these early auspicious results, phase I and II clinical trials are now in progress (Andres et al. 2008a; Locatelli et al. 2009; Onteniente and Polentes 2011; Wechsler 2009) where a positive outcome will bring us closer to a much needed new therapeutic strategy for stroke. Understanding the mechanism of action of the transplanted cells will facilitate the successful translation of cell transplantation strategies to the clinic. Here we discuss the effects of transplanted cells on brain plasti
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