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Wild-type bone marrow transplant partially reverses neuroinflammation in progranulin-deficient mice
- Source :
- Laboratory Investigation. 94:1224-1236
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Laboratory Investigation
- Accession number :
- edsair.doi.dedup.....c30870172b25cb9f838e2c3272d40a68