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. Though intra-arterial injection is expected to deliver transplanted cells mor...

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Bibliographic Details
Published in:Translational research : the journal of laboratory and clinical medicine 2016-10, Vol.176, p.69-80
Main Authors: Kasahara, Yukiko, PhD, Yamahara, Kenichi, MD, Soma, Toshihiro, MD, Stern, David M., MD, Nakagomi, Takayuki, MD, Matsuyama, Tomohiro, MD, Taguchi, Akihiko, MD
Format: Article
Language:English
Subjects:
AC133 Antigen - metabolism
Administration, Intravenous
Animals
Atrophy
Behavior, Animal
Bone Marrow Cells - cytology
Brain - pathology
Brain - physiopathology
Cell Count
Disease Models, Animal
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - cytology
Humans
Injections, Intra-Arterial
Internal Medicine
Male
Mice, SCID
Microvessels - pathology
Stroke - pathology
Stroke - therapy
Treatment Outcome
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Summary: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. Though 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 post-stroke 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.
ISSN:1931-5244
1878-1810
DOI:10.1016/j.trsl.2016.04.003