title: Intracerebral injection of human mesenchymal stem cells impacts cerebral microvasculature after experimental stroke: MRI study.
abstract: Stroke, the leading cause of disability, lacks treatment beyond thrombolysis. The acute injection of human mesenchymal stem cells (hMSCs) provides a benefit which could be mediated by an enhancement of angiogenesis. A clinical autologous graft requires an hMSC culture delay incompatible with an acute administration. This study evaluates the cerebral microvascular changes after a delayed injection of hMSCs. At day 8 after middle cerebral artery occlusion (MCAo), two groups of rats received an intracerebral injection in the damaged brain of either 10 μL of cell suspension medium (MCAo-PBS, n = 4) or 4 × 10⁵ hMSCs (MCAo-hMSC, n = 5). Two control groups of healthy rats underwent the same injection procedures in the right hemisphere (control-PBS, n = 6; control-hMSC, n = 5). The effect of hMSCs on the microvasculature was assessed by MRI using three parameters: apparent diffusion coefficient (ADC), cerebral blood volume (CBV) and vessel size index (VSI). At day 9, eight additional rats were euthanised for a histological study of the microvascular parameters (CBV, VSI and vascular fraction). No ADC difference was observed between MCAo groups. One day after intracerebral injection, hMSCs abolished the CBV increase observed in the lesion (MCAo-hMSC: 1.7 ± 0.1% versus MCAo-PBS: 2.2 ± 0.2%) and delayed the VSI increase (vasodilation) secondary to cerebral ischaemia. Histological analysis at day 9 confirmed that hMSCs modified the microvascular parameters (CBV, VSI and vascular fraction) in the lesion. No ADC, CBV or VSI differences were observed between control groups. At the stroke post-acute phase, hMSC intracerebral injection rapidly and transiently modifies the cerebral microvasculature. This microvascular effect can be monitored in vivo by MRI.
authors.affiliation: INSERM, U836, Grenoble, France. anaick.moisan@gmail.com
authors.forename: Anaïck
authors.initials: A
authors.lastname: Moisan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pannetier
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Grillon
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Richard
authors.forename: Florence
authors.initials: F
authors.lastname: de Fraipont
authors.forename: Chantal
authors.initials: C
authors.lastname: Rémy
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Barbier
authors.forename: Olivier
authors.initials: O
authors.lastname: Detante
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000209:etiology; D054022:Cerebrum / Q000098:blood supply* / Q000473:pathology*; D004058:Diffusion; D006801:Humans; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D055806:Microvessels / Q000473:pathology*; D051381:Rats; D020521:Stroke / Q000150:complications / Q000473:pathology / Q000628:therapy*