title: Neuroprotective properties of marrow-isolated adult multilineage-inducible cells in rat hippocampus following global cerebral ischemia are enhanced when complexed to biomimetic microcarriers.
abstract: Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of marrow-isolated adult multilineage-inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation and rats subjected to asphyxial cardiac arrest. We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Naïve and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after oxygen and glucose deprivation and asphyxial cardiac arrest, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed βIII-tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells.
authors.affiliation: Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Garbayo
authors.forename: Ami P
authors.initials: AP
authors.lastname: Raval
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Curtis
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.forename: Lourdes A
authors.initials: LA
authors.lastname: Gomez
authors.forename: Gianluca
authors.initials: G
authors.lastname: D'Ippolito
authors.forename: Teresita
authors.initials: T
authors.lastname: Reiner
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Stable
authors.forename: Guy A
authors.initials: GA
authors.lastname: Howard
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Perez-Pinzon
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
authors.forename: Paul C
authors.initials: PC
authors.lastname: Schiller
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002545:Brain Ischemia / Q000473:pathology* / Q000628:therapy*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D039902:Multipotent Stem Cells / Q000166:cytology*; D009474:Neurons / Q000473:pathology; D009924:Organ Culture Techniques; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D014183:Transplantation, Heterologous / Q000379:methods; D055815:Young Adult
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid