Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells
Summary: Alzheimer’s disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD ph...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009671 |
| _version_ | 1797731104721993728 |
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| author | Priyanka Mishra Alexander Silva Jay Sharma Jacqueline Nguyen Donald P. Pizzo Denise Hinz Debashis Sahoo Stephanie Cherqui |
| author_facet | Priyanka Mishra Alexander Silva Jay Sharma Jacqueline Nguyen Donald P. Pizzo Denise Hinz Debashis Sahoo Stephanie Cherqui |
| author_sort | Priyanka Mishra |
| collection | DOAJ |
| description | Summary: Alzheimer’s disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of β-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to “disease-associated microglia” in the cortex and “neurodegeneration-associated endothelial cells” in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease. |
| first_indexed | 2024-03-12T11:53:55Z |
| format | Article |
| id | doaj.art-a655da2955ba4d05968d702555cfd25e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:55Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a655da2955ba4d05968d702555cfd25e2023-08-31T05:02:19ZengElsevierCell Reports2211-12472023-08-01428112956Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cellsPriyanka Mishra0Alexander Silva1Jay Sharma2Jacqueline Nguyen3Donald P. Pizzo4Denise Hinz5Debashis Sahoo6Stephanie Cherqui7Department of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USADepartment of Pathology, University of California, San Diego, La Jolla, CA, USAFlow Cytometry Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Department of Computer Science and Engineering, University of California, La Jolla, La Jolla, CA, USA; Moores Comprehensive Cancer Center, University of California, La Jolla, La Jolla, CA, USADepartment of Pediatrics, University of California, San Diego, La Jolla, CA, USA; Corresponding authorSummary: Alzheimer’s disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of β-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to “disease-associated microglia” in the cortex and “neurodegeneration-associated endothelial cells” in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease.http://www.sciencedirect.com/science/article/pii/S2211124723009671CP: Stem cell researchCP: Neuroscience |
| spellingShingle | Priyanka Mishra Alexander Silva Jay Sharma Jacqueline Nguyen Donald P. Pizzo Denise Hinz Debashis Sahoo Stephanie Cherqui Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells Cell Reports CP: Stem cell research CP: Neuroscience |
| title | Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells |
| title_full | Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells |
| title_fullStr | Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells |
| title_full_unstemmed | Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells |
| title_short | Rescue of Alzheimer’s disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells |
| title_sort | rescue of alzheimer s disease phenotype in a mouse model by transplantation of wild type hematopoietic stem and progenitor cells |
| topic | CP: Stem cell research CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723009671 |
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