title: Effects of mesenchymal stem cell therapy, in association with pharmacologically active microcarriers releasing VEGF, in an ischaemic stroke model in the rat.
abstract: Few effective therapeutic interventions are available to limit brain damage and functional deficits after ischaemic stroke. Within this context, mesenchymal stem cell (MSC) therapy carries minimal risks while remaining efficacious through the secretion of trophic, protective, neurogenic and angiogenic factors. The limited survival rate of MSCs restricts their beneficial effects. The usefulness of a three-dimensional support, such as a pharmacologically active microcarrier (PAM), on the survival of MSCs during hypoxia has been shown in vitro, especially when the PAMs were loaded with vascular endothelial growth factor (VEGF). In the present study, the effect of MSCs attached to laminin-PAMs (LM-PAMs), releasing VEGF or not, was evaluated in vivo in a model of transient stroke. The parameters assessed were infarct volume, functional recovery and endogenous cellular reactions. LM-PAMs induced the expression of neuronal markers by MSCs both in vitro and in vivo. Moreover, the prolonged release of VEGF increased angiogenesis around the site of implantation of the LM-PAMs and facilitated the migration of immature neurons towards the ischaemic tissue. Nonetheless, MSCs/LM-PAMs-VEGF failed to improve sensorimotor functions. The use of LM-PAMs to convey MSCs and to deliver growth factors could be an effective strategy to repair the brain damage caused by a stroke.
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France. Electronic address: quittet@cyceron.fr.
authors.forename: Marie-Sophie
authors.initials: MS
authors.lastname: Quittet
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Touzani
authors.affiliation: INSERM U1066, MINT "Bio-inspired Micro and Nanomedicine", F-49933 Angers, France; LUNAM Université, F-49933 Angers, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sindji
authors.affiliation: LUNAM Université, F-49933 Angers, France; Plateforme PACeM (Plateforme d'Analyse Cellulaire et Moléculaire), SFR ICAT4208, F-49933 Angers, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cayon
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Fillesoye
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Divoux
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Léna
authors.initials: L
authors.lastname: Marteau
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Lecocq
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Roussel
authors.affiliation: INSERM U1066, MINT "Bio-inspired Micro and Nanomedicine", F-49933 Angers, France; LUNAM Université, F-49933 Angers, France.
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Université de Caen Basse-Normandie, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy group, GIP CYCERON, Bd Henri Becquerel, BP5229, F-14074 Caen cedex, France; Normandie Univ, F-14032 Caen cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001808:Blood Vessels / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004337:Drug Carriers / Q000737:chemistry*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007797:Laminin / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000089622:Doublecortin Domain Proteins; D004337:Drug Carriers; D007797:Laminin; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Mesenchymal stem cells; Pharmacologically active microcarriers; Stroke; VEGF