Mesenchymal Lineage Stem Cells Have Pronounced Anti-Inflammatory Effects in the Twitcher Mouse Model of Krabbe's Disease
| Autor: | Jessica Klopf-Eiermann, Cynthia B. Ripoll, Su Chen Li, Amy F. Lin, Shijia Zhang, Bruce A. Bunnell, Brittni A. Scruggs, Michelle E. Eagle, Marjorie McCants, Helen Paige Leonard, Xavier Alvarez, Jeffrey M. Gimble, Mette Flaat, Yu Teh Li, Jeanne M. Fisher-Perkins, Cynthia B. Trygg |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Green Fluorescent Proteins Nitric Oxide Synthase Type II Adipose tissue Inflammation Biology Mesenchymal Stem Cell Transplantation Article Proinflammatory cytokine Mice Bone Marrow Internal medicine Galactosylceramidase medicine Animals Humans Cell Lineage Gene Expression Profiling Mesenchymal stem cell Leukodystrophy Mesenchymal Stem Cells Cell Biology medicine.disease Leukodystrophy Globoid Cell Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology Adipose Tissue Immunology Molecular Medicine Bone marrow medicine.symptom Stem cell Lysosomes Developmental Biology |
| Zdroj: | Stem Cells. 29:67-77 |
| ISSN: | 1549-4918 1066-5099 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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