Abstract

Multipotent progenitor cells (MPCs), developed by Dr. Verfaillie and co-workersat the University of Minnesota, appear to have the properties which make them highly suitableas a stem cell therapy. Athersys, Inc. has the proprietary rights to these cells. We have recentlydeveloped a collaborative relationship with Athersys, Inc. which has developed manufacturingtechniques to make these cells available for clinical use. Athersys, Inc. will supply these cells to us.Our preliminary data in rodents indicate that these cells are quite promising as a therapy for stroke. Inorder to develop the utility of these cells in stroke, we propose a translational protocol. The proposedset of experiments will serve as the preclinical basis for proceeding with transplantation of MPCs inischemic stroke patients. Feasibility, safety, and optimal MFC dose and transplantation timing poststrokefor producing efficacy in rodent models of adult ischemic stroke will be examined. Thefollowing specific aims will serve as milestones, with 'go and no-go' criteria.
Specific Aim 1 : Determine the 'long-term' (i.e., 6 months post-transplantation) efficacy of IV ratMPCs in transient middle cerebral artery occlusion model.
Specific Aim 2 : Evaluate the long-term efficacy of IV human MPCs produced by Athersys, Inc.according to GMP manufacturing protocols in a GLP xenogeneic transient middle cerebralartery occlusion model.
Specific Aim 3 : Assess the efficacy of IV human MPCs to achieve long-term behavioralbenefits in male and female, and adult and aged rats exposed to transient middle cerebralartery occlusion model.
Specific Aim 4 : Demonstrate the efficacy of IV human MPCs to achieve long-term behavioralbenefits in permanent middle cerebral artery ligation model.
Specific Aim 5 : Characterize stem cell histocompatibility in allogeneic rat MPCs andxenogeneic human MPCs to further provide safety of IV MPCs in rat ischemic stroke model.
Specific Aim 6 : Conduct IND FDA preparation meetings and assemble documents for filingIND for stem cell therapy in ischemic stroke.This proposal extends our scientific platform for determining the benefit of stem cell therapy in stroke.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01NS055914-01A2
Application #
7695963
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
2008-08-01
Project End
2013-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
1
Fiscal Year
2008
Total Cost
$700,496
Indirect Cost

  Institution

Name
Georgia Regents University
Department
Type
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912

  Publications

Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka et al. (2013) Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site. PLoS One 8:e74857
Dailey, Travis; Mosley, Yusef; Pabon, Mibel et al. (2013) Advancing critical care medicine with stem cell therapy and hypothermia for cerebral palsy. Neuroreport 24:1067-71
Borlongan, Cesar V; Burns, Jack; Tajiri, Naoki et al. (2013) Epidemiological survey-based formulae to approximate incidence and prevalence of neurological disorders in the United States: a meta-analysis. PLoS One 8:e78490
Dailey, Travis; Tajiri, Naoki; Kaneko, Yuji et al. (2013) Regeneration of neuronal cells following cerebral injury. Front Neurol Neurosci 32:54-61
Shinozuka, Kazutaka; Dailey, Travis; Tajiri, Naoki et al. (2013) Stem Cells for Neurovascular Repair in Stroke. J Stem Cell Res Ther 4:12912
Tajiri, Naoki; Dailey, Travis; Metcalf, Christopher et al. (2013) In vivo animal stroke models: a rationale for rodent and non-human primate models. Transl Stroke Res 4:308-21
Kaneko, Yuji; Tajiri, Naoki; Shinozuka, Kazutaka et al. (2012) Cell therapy for stroke: emphasis on optimizing safety and efficacy profile of endothelial progenitor cells. Curr Pharm Des 18:3731-4
Glover, Loren E; Tajiri, Naoki; Weinbren, Nathan L et al. (2012) A Step-up Approach for Cell Therapy in Stroke: Translational Hurdles of Bone Marrow-Derived Stem Cells. Transl Stroke Res 3:90-8
Borlongan, C V (2011) Bone marrow stem cell mobilization in stroke: a 'bonehead' may be good after all! Leukemia 25:1674-86
Borlongan, Cesar V; Glover, Loren E; Tajiri, Naoki et al. (2011) The great migration of bone marrow-derived stem cells toward the ischemic brain: therapeutic implications for stroke and other neurological disorders. Prog Neurobiol 95:213-28

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