title: Vascular fate of adipose tissue-derived adult stromal cells in the ischemic murine brain: A combined imaging-histological study.
abstract: Increasing evidence indicates that fat tissue can provide a novel source of progenitor cells with therapeutic potential. Here, the fate of adipose tissue-derived stromal cells (ADSCs) transplanted into the mouse ischemic cortex was monitored in the long term using in vivo imaging, and subsequently characterized. The left middle cerebral artery (MCA) was occluded in C57BL/6J mice equipped with a closed cranial window chronically implanted over the left parietal cortex (n = 20). ADSCs expressing the green fluorescent protein (GFP) (approximately 18 x 10(3) cells in 0.5 microl) were transplanted into the ipsilateral cortex, 24 h after MCA occlusion. GFP+-ADSCs were monitored through the window using confocal fluorescence microscopy to assess their single fate in vivo. Co-localization of GFP with vascular, neuronal, glial or proliferation markers was investigated immunohistochemically. Repeated in vivo imaging revealed that GFP+-ADSCs migrated over 1 week toward the lesion, survived for at least 4 weeks, and exhibited a particular tropism for vessels. About 5% of the transplanted GFP+-ADSCs were scattered in the peri-ischemic area on histological sections. Immunohistochemistry evidenced that perivascular GFP+-ADSCs enfolded CD31-labeled endothelial cells, always outside their basal lamina, and occasionally expressed smooth muscle alpha-actin. Less than 1% GFP and BrdU co-labeling indicated a low proliferation rate of ADSCs. These results demonstrate that cerebral ischemia induces ADSCs survival, migration toward the lesion, especially toward microvessels, and occasional differentiation into smooth muscle cells.
authors.affiliation: Cardiovascular Research Centre Lariboisière, INSERM U 689, Université Paris 7; IFR 139, Paris, France. nathalie.kubis@lrb.aphp.fr
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kubis
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tomita
authors.forename: Alexy
authors.initials: A
authors.lastname: Tran-Dinh
authors.forename: Valérie
authors.initials: V
authors.lastname: Planat-Benard
authors.forename: Mireille
authors.initials: M
authors.lastname: André
authors.forename: Bartosz
authors.initials: B
authors.lastname: Karaszewski
authors.forename: Ludovic
authors.initials: L
authors.lastname: Waeckel
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Jacques
authors.initials: J
authors.lastname: Seylaz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pinard
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002545:Brain Ischemia / Q000601:surgery*; D002465:Cell Movement; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*