title: The therapeutic potential of human multipotent mesenchymal stromal cells combined with pharmacologically active microcarriers transplanted in hemi-parkinsonian rats.
abstract: Multipotent mesenchymal stromal cells (MSCs) raise great interest for brain cell therapy due to their ease of isolation from bone marrow, their immunomodulatory and tissue repair capacities, their ability to differentiate into neuronal-like cells and to secrete a variety of growth factors and chemokines. In this study, we assessed the effects of a subpopulation of human MSCs, the marrow-isolated adult multilineage inducible (MIAMI) cells, combined with pharmacologically active microcarriers (PAMs) in a rat model of Parkinson's disease (PD). PAMs are biodegradable and non-cytotoxic poly(lactic-co-glycolic acid) microspheres, coated by a biomimetic surface and releasing a therapeutic protein, which acts on the cells conveyed on their surface and on their microenvironment. In this study, PAMs were coated with laminin and designed to release neurotrophin 3 (NT3), which stimulate the neuronal-like differentiation of MIAMI cells and promote neuronal survival. After adhesion of dopaminergic-induced (DI)-MIAMI cells to PAMs in vitro, the complexes were grafted in the partially dopaminergic-deafferented striatum of rats which led to a strong reduction of the amphetamine-induced rotational behavior together with the protection/repair of the nigrostriatal pathway. These effects were correlated with the increased survival of DI-MIAMI cells that secreted a wide range of growth factors and chemokines. Moreover, the observed increased expression of tyrosine hydroxylase by cells transplanted with PAMs may contribute to this functional recovery.
authors.affiliation: Inserm, U646, 10 rue André Boquel, Angers, F49100 France.
authors.forename: Gaëtan J-R
authors.initials: GJ
authors.lastname: Delcroix
authors.forename: Elisa
authors.initials: E
authors.lastname: Garbayo
authors.forename: Laurence
authors.initials: L
authors.lastname: Sindji
authors.forename: Olivier
authors.initials: O
authors.lastname: Thomas
authors.forename: Claire
authors.initials: C
authors.lastname: Vanpouille-Box
authors.forename: Paul C
authors.initials: PC
authors.lastname: Schiller
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D007797:Laminin / Q000737:chemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008863:Microspheres; D039902:Multipotent Stem Cells / Q000166:cytology*; D020933:Neurotrophin 3 / Q000737:chemistry / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism / Q000628:therapy*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D007797:Laminin; D020933:Neurotrophin 3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid