title: Placental mesenchymal stromal cells induced into neurotrophic factor-producing cells protect neuronal cells from hypoxia and oxidative stress.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) may be useful in a range of clinical applications. The placenta has been suggested as an abundant, ethically acceptable, less immunogenic and easily accessible source of MSC. The aim of this study was to evaluate the capacity of induced placental MSC to differentiate into neurotrophic factor-producing cells (NTF) and their protective effect on neuronal cells.
  
  
  METHODS
  MSC were isolated from placentas and characterized by fluorescence-activated cell sorting (FACS). The cells underwent an induction protocol to differentiate them into NTF. Analysis of the cellular differentiation was done using polymerase chain reactions (PCR), immunocytochemical staining and enzyme-linked immunosorbent assays (ELISA). Conditioned media from placental MSC (PL-MSC) and differentiated MSC (PL-DIFF) were collected and examined for their ability to protect neural cells.
  
  
  RESULTS
  The immunocytochemical studies showed that the cells displayed typical MSC membrane markers. The cells differentiated into osteoblasts and adipocytes. PCR and immunohistology staining demonstrated that the induced cells expressed typical astrocytes markers and neurotrophic factors. Vascular endothelial growth factor (VEGF) levels were higher in the conditioned media from PL-DIFF compared with PL-MSC, as indicated by ELISA. Both PL-DIFF and PL-MSC conditioned media markedly protected neural cells from oxidative stress induced by H(2)O(2) and 6-hydroxydopamine. PL-DIFF conditioned medium had a superior effect on neuronal cell survival. Anti-VEGF antibodies (Bevacizumab) reduced the protective effect of the conditioned media from differentiated and undifferentiated MSC.
  
  
  CONCLUSIONS
  This study has demonstrated a neuroprotective effect of MSC of placental origin subjected to an induction differentiation protocol. These data offer the prospect of using placenta as a source for stem cell-based therapies.
authors: Department of Neurology, Hospital for Women, Rabin Medical Center, Petah Tiqwa 49100, Israel. liorshlomit@yahoo.com
authors: Shlomit
authors: S
authors: Yust-Katz
authors: Yonit
authors: Y
authors: Fisher-Shoval
authors: Yael
authors: Y
authors: Barhum
authors: Tali
authors: T
authors: Ben-Zur
authors: Ran
authors: R
authors: Barzilay
authors: Nirit
authors: N
authors: Lev
authors: Moshe
authors: M
authors: Hod
authors: Eldad
authors: E
authors: Melamed
authors: Daniel
authors: D
authors: Offen
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D002469:Cell Separation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D042461:Vascular Endothelial Growth Factor A; D006861:Hydrogen Peroxide