Clinical Trials: Intracerebral Cell Therapy in Stroke Patients
Successful experimental models of intracerebral cell transplantation to enhance neurological recovery from stroke have prompted the pursuit of early phase clinical trials. Published results of three completed studies report that intracerebral delivery of
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Douglas Kondziolka, Gillian Harrison, and Lawrence Wechsler
11.1
Introduction
The use of stem cell therapy for stroke is a burgeoning area of clinical research. Buoyed by promising studies performed in preclinical animal models of stroke, in which transplanted cells resulted in functional improvement (Borlongan et al. 1998; Chen et al. 2001a, b; Chopp and Li 2002; Guzman et al. 2008; Hicks et al. 2009; Stroemer et al. 2008), the study of intracerebral cell therapy for stroke has progressed to early phase clinical trials. Though it is clear that transplanted cells convey a functional benefit, the mechanism by which this occurs is not fully known. Transplanted cells are hypothesized to provide benefit not only directly through cell replacement of damaged tissue but also by providing trophic, neuroprotective, and immunomodulatory support. Lack of clear mechanism is but one of the challenging considerations encountered in the design of clinical trials. Particular concerns that may impact the potential success of cell therapy include the anatomy, vascular supply, timing of stroke, site and technical
D. Kondziolka, M.D., M.Sc., FRCSC (*) Professor of Neurosurgery, NYU Langone Medical Center, 530 First Ave, Suite 8R New York, NY 10016, USA Department of Neurosurgery, New York University, New York, USA Departments of Neurological Surgery and Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA e-mail: [email protected] G. Harrison, B.S. • L. Wechsler, M.D. Department of Neurosurgery, New York University, New York, USA Departments of Neurological Surgery and Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA J. Jolkkonen, P. Walczak (eds.), Cell-Based Therapies in Stroke, DOI 10.1007/978-3-7091-1175-8_11, © Springer-Verlag Wien 2013
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delivery of cell implantation, target patient population, and selection of appropriate outcome measures (Locatelli et al. 2009; Savitz et al. 2004). A variety of cell types have been investigated in experimental models and translated to clinical trials. Published trials of intracerebral cell therapy studied cells derived from embryonic carcinoma lines (Kondziolka et al. 2000, 2005), fetal porcine striatum (Savitz et al. 2005), and bone marrow (Suárez-Monteagudo et al. 2009). More recently, investigators around the world have continued to evaluate the use of both autologous marrow-derived (NCT00950521) and allogeneic cord bloodderived (NCT01438593) cells, as well as neural stem cells (NCT01151124). Current studies in the United States have focused on the use of modified marrow stromal cells (NCT01287936). This review summarizes the four published clinical trials of intracerebral cell therapy for stroke and describes the ongoing study of such therapy in the United States (Table 11.1).
11.2
Preclinical Basis for Clinical Trials
Several investigators have evaluated the use of transplanted fetal tissue, rat striatum, or cellular implants in small animal stroke models (Johansson and Grabowski 1994; Kleppner et al. 1995). Alt
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