title: Neuroprotective effect of human placenta-derived cell treatment of stroke in rats.
abstract: Human placenta-derived adherent (PDA001) cells are mesenchymal-like stem cells isolated from postpartum placenta. In this study, we tested whether intravenously infused PDA001 improves neurological functional recovery after stroke in rats. In addition, potential mechanisms underlying the PDA001-induced neuroprotective effect were investigated. Young adult male rats (2–3 months) were subjected to 2 h of middle cerebral artery occlusion (MCAo) and treated with PDA001 (4x10(6)) or vehicle controls [dextran vehicle or phosphate buffer saline (PBS)] via intravenous (IV) administration initiated at 4 h after MCAo. A battery of functional tests and measurements of lesion volume and apoptotic cells were performed. Immunostaining and ELISA assays for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and brain derived neurotrophic factor (BDNF) were performed in the ischemic brain to test the potential mechanisms underlying the neuroprotective effects of PDA001 cell treatment of stroke. PDA001 cell treatment at 4 h post stroke significantly improved functional outcome and significantly decreased lesion volume, TUNEL, and cleaved caspase 3-positive cell number in the ischemic brain, compared to MCAo-vehicle and MCAo-PBS control. Treatment of stroke with PDA001 cells also significantly increased HGF and VEGF expression in the ischemic border zone (IBZ) compared to controls. Using ELISA assays, treatment of stroke with PDA001 cells significantly increased VEGF, HGF, and BDNF levels in the ischemic brain compared to controls.
  
  
  CONCLUSIONS
  When administered intravenously at 4 h after MCAo, PDA001 cells promoted neuroprotective effects. These effects induced by PDA001 cell treatment may be related to the increase of VEGF, HGF, and BDNF expression,and a decrease of apoptosis. PDA001 cells may provide a viable cell source to treat stroke.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, MI, USA. jieli@neuro.hfh.edu
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.forename: Amjad
authors.initials: A
authors.lastname: Shehadah
authors.forename: Ajai
authors.initials: A
authors.lastname: Pal
authors.forename: Alex
authors.initials: A
authors.lastname: Zacharek
authors.forename: Xu
authors.initials: X
authors.lastname: Cui
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Cui
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Andrew
authors.initials: A
authors.lastname: Zeitlin
authors.forename: Robert
authors.initials: R
authors.lastname: Hariri
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor