title: Superselective intra-arterial umbilical cord blood administration to BM in experimental animals.
abstract: Umbilical cord blood (UCB) as a source of hematopoietic stem cells for transplantation is limited by the low number of cells and delayed engraftment. UCB cells are infused i.v. for transplantation, although only a proportion of the cells reach the BM. We investigated whether UCB could be administered safely using superselective intra-arterial (i.a.) injection. We injected human UCB (5 × 10(6)) into the aorta in rats, into the iliac artery in mice and into the femoral nutrient artery (FNA) in rabbits. We used angiography, immunohistochemistry, intravital microscopy and qPCR to assess safety end points and the distribution of injected cells. All animals showed normal behavior. No evidence of organ infarction was noted. UCB injected into the FNA of rabbits did not change the flow rates, measured by angiography. By qPCR, we found significantly higher fold-change values in the injected BM compared with i.v. injection (P=0.0087). Using intravital microscopy we visualized the mouse capillary bed during i.a. injection without cellular congestion. In summary, we show that i.a. infusion of UCB is safe and reaches an eightfold increase in engraftment in the BM compared with i.v. infusion. These studies lay the foundation for clinical trials.
authors.affiliation: 1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [2] Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden [3] Department of Radiology, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Arnberg
authors.affiliation: 1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [2] Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lundberg
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Kenne
authors.affiliation: 1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [2] Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Jaff
authors.affiliation: Bioinformatics and Expression Analysis Core Facility, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Müller
authors.affiliation: Division of Therapeutic Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Nava
authors.affiliation: Division of Therapeutic Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Kaipe
authors.affiliation: Division of Therapeutic Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Stockholm, Sweden.
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.affiliation: 1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [2] Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Holmin
mesh_terms: D000792:Angiography; D000818:Animals; D001158:Arteries / Q000473:pathology*; D044963:Biopsy, Fine-Needle; D001853:Bone Marrow / Q000473:pathology*; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley