Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice
| Autor: | C. Dirk Keene, Eiron Cudaback, Samuel R Josephsen, Macarena S. Aloi, Thomas J. Montine, Nikolas L. Jorstad, Samantha Rice, Yue Yang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Central nervous system In Vitro Techniques Biology Article Pathology and Forensic Medicine Immunomodulation Progranulins mental disorders medicine Animals Molecular Biology Neuroinflammation Bone Marrow Transplantation Granulins Cerebral Cortex Microglia Wild type Cell Biology Mice Inbred C57BL medicine.anatomical_structure Cerebral cortex Frontotemporal Dementia Immunology Intercellular Signaling Peptides and Proteins Bone marrow Stem cell Ex vivo |
| Zdroj: | Laboratory Investigation. 94:1224-1236 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2014.113 |
| Popis: | Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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