title: Human mesenchymal stromal cell transplantation modulates neuroinflammatory milieu in a mouse model of amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs), after intraparenchymal, intrathecal and endovenous administration, have been previously tested for cell therapy in amyotrophic lateral sclerosis in the SOD1 (superoxide dismutase 1) mouse. However, every administration route has specific pros and cons.
  
  
  METHODS
  We administrated human MSCs (hMSCs) in the cisterna lumbaris, which is easily accessible and could be used in outpatient surgery, in the SOD1 G93A mouse, at the earliest onset of symptoms. Control animals received saline injections. Motor behavior was checked starting from 2 months of age until the mice were killed. Animals were killed 2 weeks after transplantation; lumbar motoneurons were stereologically counted, astrocytes and microglia were analyzed and quantified after immunohistochemistry and cytokine expression was assayed by means of real-time polymerase chain reaction.
  
  
  RESULTS
  We provide evidence that this route of administration can exert strongly positive effects. Motoneuron death and motor decay were delayed, astrogliosis was reduced and microglial activation was modulated. In addition, hMSC transplantation prevented the downregulation of the anti-inflammatory interleukin-10, as well as that of vascular endothelial growth factor observed in saline-treated transgenic mice compared with wild type, and resulted in a dramatic increase in the expression of the anti-inflammatory interleukin-13.
  
  
  CONCLUSIONS
  Our results suggest that hMSCs, when intracisternally administered, can exert their paracrine potential, influencing the inflammatory response of the host.
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy. Electronic address: marina.boido@unito.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Boido
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piras
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Valsecchi
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Spigolon
authors.affiliation: Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, City of Science and Health of Turin, Regina Margherita Children's Hospital, Department of Public Health and Paediatrics, University of Torino, Torino, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Mareschi
authors.affiliation: Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, City of Science and Health of Turin, Regina Margherita Children's Hospital, Department of Public Health and Paediatrics, University of Torino, Torino, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferrero
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vizzini
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Santa
authors.initials: S
authors.lastname: Temi
authors.affiliation: ALS Centre Department of Neurology, University of Eastern Piedmont, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.affiliation: Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, City of Science and Health of Turin, Regina Margherita Children's Hospital, Department of Public Health and Paediatrics, University of Torino, Torino, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
authors.affiliation: Neuroscience Institute Cavalieri Ottolenghi, Department of Neuroscience, University of Torino, Torino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D017628:Microglia / Q000473:pathology; D008884:Milieu Therapy; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology
keywords: cell therapy; cisterna lumbaris; cytokines; microglia; motoneuron