title: Transplantation of hematopoietic stem cells: intra-arterial versus intravenous administration impacts stroke outcomes in a murine model.
abstract: Based on results of hematopoietic stem cell transplantation in animal models of stroke, clinical trials with hematopoietic stem cells administered intra-arterially or intravenously have been initiated in patients. Although intra-arterial injection is expected to deliver transplanted cells more directly to the ischemic tissue, the optimal route for enhancing clinical outcomes has not been identified in the setting of stroke. In this study, we compared the therapeutic potential of intra-arterial versus intravenous injection of bone marrow derived-mononuclear cells (BM-MNCs) and CD133-positive (CD133(+)) cells in a murine stroke model. We have found that intra-arterial injection of BM-MNCs exaggerates inflammation with accompanying loss of microvascular structures in poststroke brain and no improvement in cortical function. In contrast, intravenous injection of BM-MNCs did not similarly enhance inflammation and improved cortical function. Our results indicate that the optimal route of cell transplantation can vary with different cell populations and highlight possible issues that might arise with intra-arterial cell administration for acute ischemic cerebrovascular disease.
authors.affiliation: Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kasahara
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.affiliation: Department of Hematology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Soma
authors.affiliation: Executive Dean's office, University of Tennessee, Tennessee, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.affiliation: Department of Neurogenesis and CNS repair, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagomi
authors.affiliation: Department of Neurogenesis and CNS repair, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Department of Regenerative Medicine Research, Institute of Biomedical Research and Innovation, Kobe, Japan. Electronic address: taguchi@fbri.org.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D061605:Administration, Intravenous; D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D016513:Mice, SCID; D055806:Microvessels / Q000473:pathology; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen