title: Intracerebroventricular injection of encapsulated human mesenchymal cells producing glucagon-like peptide 1 prolongs survival in a mouse model of ALS.
abstract: BACKGROUND
  As pharmacological therapies have largely failed so far, stem cell therapy has recently come into the focus of ALS research. Neuroprotective potential was shown for several types of stem and progenitor cells, mainly due to release of trophic factors. In the present study, we assessed the effects of intracerebroventricular injection of glucagon-like peptide 1 (GLP-1) releasing mesenchymal stromal cells (MSC) in mutant SOD1 (G93A) transgenic mice.
  
  
  RESULTS
  To improve the neuroprotective effects of native MSC, they had been transfected with a plasmid vector encoding a GLP-1 fusion gene prior to the injection, as GLP-1 was shown to exhibit neuroprotective properties before. Cells were encapsulated and therefore protected against rejection. After intracerebroventricular injection of these GLP-1 MSC capsules in presymptomatic SOD1 (G93A) mice, we assessed possible protective effects by survival analysis, measurement of body weight, daily monitoring and evaluation of motor performance by rotarod and footprint analyses. Motor neuron numbers in the spinal cord as well as the amount of astrocytosis, microglial activation, heat shock response and neuronal nitric oxide synthase (nNOS) expression were analyzed by immunohistological methods. Treatment with GLP-1 producing MSC capsules significantly prolonged survival by 13 days, delayed symptom onset by 15 days and weight loss by 14 days and led to significant improvements in motor performance tests compared to vehicle treated controls. Histological data are mainly in favour of anti-inflammatory effects of GLP-1 producing MSC capsules with reduced detection of inflammatory markers and a significant heat shock protein increase.
  
  
  CONCLUSIONS
  Intracerebroventricular injection of GLP-1 MSC capsules shows neuroprotective potential in the SOD1 (G93A) mouse model.
authors: Department of Neurology, Hannover Medical School, Hannover, Germany. Knippenberg.Sarah@mh-hannover.de
authors: Sarah
authors: S
authors: Knippenberg
authors: Nadine
authors: N
authors: Thau
authors: Reinhard
authors: R
authors: Dengler
authors: Thomas
authors: T
authors: Brinker
authors: Susanne
authors: S
authors: Petri
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D052216:Glucagon-Like Peptide 1; D052248:Nitric Oxide Synthase Type I; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1