title: Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery.
abstract: Intravascular cell therapy is a promising approach for the treatment of stroke. However, high accumulation of cells to lungs and other filtering organs is a major concern after intravenous (i.v.) cell transplantation. This can be circumvented by intra-arterial (i.a.) cell infusion, which improves homing of cells to the injured brain. We studied the effect of i.a. delivery of human bone marrow-derived mesenchymal cells (BMMSCs) on behavioral and histological outcome in rats after middle cerebral artery occlusion (MCAO). Sixty male Wistar rats were subjected to transient MCAO (60 min) or sham-operation. BMMSCs (1×10(6)) were infused into the external carotid artery on postoperative day 2 or 7. Histology performed after a 42-day follow-up did not detect any human cells (MAB1281) in the ischemic brain. Endothelial cell staining with RECA-1 revealed a significant increase in the number of blood vessels in the perilesional cortex in MCAO rats treated with cells on postoperative day 7. Behavioral recovery as assessed in three tests, sticky label, cylinder and Montoya's staircase, was not improved by human BMMSCs during the follow-up. In conclusion, human BMMSCs did not improve functional recovery in MCAO rats despite effective initial homing to the ischemic hemisphere and enhanced angiogenesis, when strict behavioral tests not affected by repeated testing and compensation were utilized.
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland.
authors.forename: Bhimashankar
authors.initials: B
authors.lastname: Mitkari
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Nitzsche
authors.affiliation: Finnish Red Cross Blood Service, Advanced Therapies and Product Development, Helsinki, Finland.
authors.forename: Erja
authors.initials: E
authors.lastname: Kerkelä
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kuptsova
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Huttunen
authors.affiliation: Finnish Red Cross Blood Service, Advanced Therapies and Product Development, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Nystedt
authors.affiliation: Finnish Red Cross Blood Service, Advanced Therapies and Product Development, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Korhonen
authors.affiliation: Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland. Electronic address: jukka.jolkkonen@uef.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D004195:Disease Models, Animal; D005121:Extremities / Q000503:physiopathology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D007261:Infusions, Intra-Arterial; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D018396:Mucin-1 / Q000378:metabolism; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018396:Mucin-1
keywords: Angiogenesis; Behavioral recovery; Cell therapy; Cerebral ischemia; Human bone marrow derived mesenchymal cells; Intravascular delivery