title: Effect of intrastriatal mesenchymal stromal cell injection on progression of a murine model of Krabbe disease.
abstract: One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.
authors.affiliation: Nutritional Neuroscience and Aging, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA. shawna.wicks@pbrc.edu
authors.forename: Shawna E
authors.initials: SE
authors.lastname: Wicks
authors.forename: Heaven
authors.initials: H
authors.lastname: Londot
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dowden
authors.forename: Jessica
authors.initials: J
authors.lastname: Klopf-Eiermann
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Fisher-Perkins
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Trygg
authors.forename: Brittni A
authors.initials: BA
authors.lastname: Scruggs
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Pistell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D058948:Cell Tracking / Q000379:methods / Q000706:statistics & numerical data; D003342:Corpus Striatum / Q000601:surgery*; D004195:Disease Models, Animal; D018450:Disease Progression; D005684:Gait; D005838:Genotype; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis / Q000628:therapy*; D018782:Maze Learning; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D045442:Rotarod Performance Test / Q000706:statistics & numerical data