title: Intravenous Injection of Clinical Grade Human MSCs After Experimental Stroke: Functional Benefit and Microvascular Effect.
abstract: Stroke is the leading cause of disability in adults. Many current clinical trials use intravenous (IV) administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms of action involved after an IV injection of human BM-MSCs (hBM-MSCs) at a subacute phase of stroke. Rats underwent a transient middle cerebral artery occlusion (MCAo) or a surgery without occlusion (sham) at day 0 (D0). At D8, rats received an IV injection of 3 million hBM-MSCs or PBS-glutamine. In a longitudinal behavioral follow-up, we showed delayed somatosensory and cognitive benefits 4 to 7 weeks after hBM-MSC injection. In a separate longitudinal in vivo magnetic resonance imaging (MRI) study, we observed an enhanced vascular density in the ischemic area 2 and 3 weeks after hBM-MSC injection. Histology and quantitative polymerase chain reaction (qPCR) revealed an overexpression of angiogenic factors such as Ang1 and transforming growth factor-1 (TGF-1) at D16 in hBM-MSC-treated MCAo rats compared to PBS-treated MCAo rats. Altogether, delayed IV injection of hBM-MSCs provides functional benefits and increases cerebral angiogenesis in the stroke lesion via a release of endogenous angiogenic factors enhancing the stabilization of newborn vessels. Enhanced angiogenesis could therefore be a means of improving functional recovery after stroke.
authors.forename: Anack
authors.initials: A
authors.lastname: Moisan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Favre
authors.forename: Claire
authors.initials: C
authors.lastname: Rome
authors.forename: Florence
authors.initials: F
authors.lastname: De Fraipont
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Grillon
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coquery
authors.forename: Herv
authors.initials: H
authors.lastname: Mathieu
authors.forename: Virginie
authors.initials: V
authors.lastname: Mayan
authors.forename: Bernadette
authors.initials: B
authors.lastname: Naegele
authors.forename: Marc
authors.initials: M
authors.lastname: Hommel
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Richard
authors.forename: Emmanuel Luc
authors.initials: EL
authors.lastname: Barbier
authors.forename: Chantal
authors.initials: C
authors.lastname: Remy
authors.forename: Olivier
authors.initials: O
authors.lastname: Detante
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020521:Stroke / Q000473:pathology* / Q000628:therapy; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D053781:Transforming Growth Factor beta2