title: Intrahippocampal transplantation of mesenchymal stromal cells promotes neuroplasticity.
abstract: OBJECTIVE
  Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus.
  
  
  METHODS
  Rat bone marrow-derived MSC were labeled with very small superparamagnetic iron oxide particles (VSOP), which allowed for non-invasive graft localization by magnetic resonance imaging (MRI). Moreover, MSC were transduced with lentiviral vectors to express the green fluorescent protein (GFP). The effects of bilateral MSC transplantation on hippocampal cellular plasticity were assessed using the thymidine analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU). Behavioral testing was performed to examine the consequences of intrahippocampal MSC transplantation on locomotion, learning and memory, and anxiety-like and depression-like behavior.
  
  
  RESULTS
  We found that intrahippocampal transplantation of MSC resulted in enhanced neurogenesis despite short-term graft survival. In contrast, systemic administration of the selective serotonin re-uptake inhibitor citalopram increased cell survival but did not affect cell proliferation. Intrahippocampal transplantation of MSC did not impair behavioral functions in rats, but only citalopram exerted anti-depressant effects.
  
  
  CONCLUSIONS
  This is the first study to examine the effects of intrahippocampal transplantation of allogeneic MSC on hippocampal structural plasticity and behavioral functions in rats combined with non-invasive cell tracking by MRI. We found that iron oxide nanoparticles can be used to detect transplanted MSC in the brain. Although graft survival was short, intrahippocampal transplantation of MSC resulted in long-term changes in hippocampal plasticity. Our results suggest that MSC can be used to stimulate adult neurogenesis.
authors: Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Berlin, Germany.
authors: Nicolas
authors: N
authors: Coquery
authors: Armin
authors: A
authors: Blesch
authors: Albrecht
authors: A
authors: Stroh
authors: Francisco
authors: F
authors: Fernández-Klett
authors: Julia
authors: J
authors: Klein
authors: Christine
authors: C
authors: Winter
authors: Josef
authors: J
authors: Priller
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D015283:Citalopram / Q000008:administration & dosage; D005290:Ferric Compounds / Q000737:chemistry; D006624:Hippocampus / Q000166:cytology / Q000637:transplantation*; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D009473:Neuronal Plasticity; D051381:Rats
chemical_list: D005290:Ferric Compounds; D015283:Citalopram; C000499:ferric oxide