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Article first published online: 28 JAN 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 1, pages 67–77, January 2011
How to Cite
Ripoll, C. B., Flaat, M., Klopf-Eiermann, J., Fisher-Perkins, J. M., Trygg, C. B., Scruggs, B. A., McCants, M. L., Leonard, H. P., Lin, A. F., Zhang, S., Eagle, M. E., Alvarez, X., Li, Y. T., Li, S. C., Gimble, J. M. and Bunnell, B. A. (2011), Mesenchymal Lineage Stem Cells Have Pronounced Anti-Inflammatory Effects in the Twitcher Mouse Model of Krabbe's Disease. STEM CELLS, 29: 67–77. doi: 10.1002/stem.555
Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or National Institutes of Health.
Author contributions: C.B.R.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; M.F.: conception and design, collection and/or assembly of data, data analysis and interpretation; J.K.-E.: collection and/or assembly of data; J.M.F.-P.: collection and/or assembly of data; C.B.T.: collection and/or assembly of data; B.A.S.: collection and/or assembly of data; M.L.M.: collection and/or assembly of data; H.P.L.: collection and/or assembly of data; A.F.L.: collection and/or assembly of data; S.Z.: collection and/or assembly of data; M.E.E.: collection and/or assembly of data; X.A.: collection and/or assembly of data; Y.T.L: collection and/or assembly of data; S.C.L.: collection and/or assembly of data; J.M.G.: conception and design; B.A.B.: conception and design, financial support, administrative support, final approval of manuscript.
First published online in STEM CELLS EXPRESS November 9, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 28 JAN 2011
- Article first published online: 28 JAN 2011
- Accepted manuscript online: 9 NOV 2010 10:13AM EST
- Manuscript Accepted: 14 OCT 2010
- Manuscript Received: 2 JUN 2010
- Stem cells;
- Bone marrow;
- Adipose tissue;
- Krabbe's Disease;
- Globoid cell leukodystrophy;
- Twitcher mouse;
The twitcher mouse is an animal model of Krabbe's disease (KD), which is a neurodegenerative lysosomal storage disorder resulting from the absence of functional lysosomal enzyme galactocerebrosidase (GALC). This disease affects the central and peripheral nervous systems and in its most severe form results in death before the age of 2 in humans and approximately 30–40 days in mice. This study evaluates the effect of intracerebroventricular administration of mesenchymal stem cells derived from adipose tissue (ASCs) and bone marrow (BMSCs) on the pathology of KD. Subsequent to the intracerebroventricular injection of ASCs or BMSCs on postnatal day (PND) 3–4, body weight, lifespan, and neuromotor function were evaluated longitudinally beginning on PND15. At sacrifice, tissues were harvested for analysis of GALC activity, presence of myelin, infiltration of macrophages, microglial activation, inflammatory markers, and cellular persistence. Survival analysis curves indicate a statistically significant increase in lifespan in stem cell-treated twitcher mice as compared with control twitcher mice. Body weight and motor function were also improved compared with controls. The stem cells may mediate some of these benefits through an anti-inflammatory mechanism because the expression of numerous proinflammatory markers was downregulated at both transcriptional and translational levels. A marked decrease in the levels of macrophage infiltration and microglial activation was also noted. These data indicate that mesenchymal lineage stem cells are potent inhibitors of inflammation associated with KD progression and offer potential benefits as a component of a combination approach for in vivo treatment by reducing the levels of inflammation. STEM CELLS 2011;29:67–77