Intravascular Stem Cell Transplantation for Stroke
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CELL-BASED THERAPIES FOR STROKE
Intravascular Stem Cell Transplantation for Stroke Angela M. Auriat & Sahar Rosenblum & Tenille N. Smith & Raphael Guzman
Received: 27 June 2011 / Accepted: 13 July 2011 / Published online: 4 August 2011 # Springer Science+Business Media, LLC 2011
Abstract Stroke is the third leading cause of death and the leading cause of adult disability in North America. Emphasis has been placed on developing treatments that reduce the devastating long-term impacts of this disease, and preclinical research on stem cell therapy has demonstrated promising results. However, questions about the optimal cell delivery method and timing of cell transplantation are not fully answered. Recent findings suggest that intravascular stem cell delivery is a safe and efficacious alternative to stereotactic cell injections. It also offers advantages should repeat treatments prove beneficial. Recent reports further suggest that intra-arterial injection results in a wider distribution of cells throughout the stroked hemisphere with a significantly greater cell engraftment compared to intravenous injection. In this review, we describe the benefits and potential risks associated with intravascular stem cell delivery and compare intra-arterial to intravenous cell transplantation methods. We discuss the importance of cell biodistribution and timing of transplantation in driving cell survival. We examine current proposed mechanisms involved in cell migration and functional recovery and discuss future directions for intravascular stem cell therapy research. Keywords Stroke . Stem cells . Neural stem cells . Intravascular . Intra-arterial . Cell therapy
A. M. Auriat : S. Rosenblum : T. N. Smith : R. Guzman (*) Department of Neurosurgery and Division of Pediatric Neurosurgery, Stanford University School of Medicine, and Lucile Packard Children’s Hospital, 300 Pasteur Drive, R211, Stanford, CA 94305-5327, USA e-mail: [email protected]
Introduction Stroke is the third leading cause of mortality and the leading cause of disability in North America. The significant cost to the health care system will continue to increase as the population ages and the prevalence of risk factors grow (obesity, hypertension) [1]. Despite great efforts aimed at developing treatments for stroke, only one intervention has been approved for clinical use [2]. While intravenous tissue plasminogen activator (tPA) may provide some benefits for stroke, only about 2% of ischemic stroke patients are eligible to receive tPA given the limited time window available for effective thrombolysis [3]. Interventions focused on improving recovery in the post-acute period are needed, and stem cell therapies are a promising solution. Cell-based therapies have shown a considerable ability to improve functional outcome when administered after experimental stroke [4, 5]. Many types of stem cells, including mesenchymal stem cells (MSCs)/bone marrow stromal cells (BMSCs), umbilical cord blood cells (UCBCs), embryonic stem cells (ESCs), fetal neural stem cells (FNSCs)
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