Genetically engineered microglia-like cells have therapeutic potential for neurodegenerative disease
Plasschaert, R. N.; DeAndrade, M. P.; Hull, F.; Nguyen, Q.; Peterson, T.; Yan, A.; Loperfido, M.; Baricordi, C.; Barbarossa, L.; Yoon, J. K.; Dogan, Y.; Unnisa, Z.; Schindler, J. W.; van Til, N. P.; Biasco, L.; Mason, C.
Show abstract
Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) results in the engraftment of genetically modified microglia-like cells (MLCs) in the brain. While HSPC-GT has shown a clear neurological benefit in the clinic for specific rare diseases, the nature of MLC engraftment in the brain and the functional characteristics of MLCs remain contentious. Here we comprehensively characterized how different routes of administration affect the engraftment and biodistribution of genetically engineered HSPC-derivatives in mice. Using high-throughput single-cell profiling, we show that MLCs bear a transcriptional signature similar to resident microglia rather than invading macrophages. However, MLCs could clearly be distinguished from resident microglia by expression of a specific set of genes. Finally, in murine models of Parkinsons disease and frontotemporal dementia, we demonstrate that MLCs can provide therapeutically relevant levels of protein to the brain, thereby potentially opening avenues of HSPC-GT to address the underlying disease etiology of these and other similar disorders.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Xenotransplantation of Human PSC-derived Microglia Creates a Chimeric Mouse Brain Model that Recapitulates Features of Adult Human Microglia 97%
- Lesion environments direct transplanted neural progenitors towards a wound repair astroglial phenotype 96%
- Glioma-neuronal circuit remodeling induces regional immunosuppression 96%
Similar papers in this journal
- Preclinical lentiviral vector-mediated hematopoietic stem and progenitor cell gene therapy corrects Pompe disease-related muscle and neurological manifestations 96%
- TALEN-mediated intron editing of HSPCs enables transgene expression restricted to the myeloid lineage 96%
- CD33 Epitope Editing Unlocks UM171-Expanded Cord Blood Grafts for AML Immunotherapy 96%
Similar papers in this journal
- Subventricular zone/white matter microglia reconstitute the empty adult microglial niche in a dynamic wave 96%
- PTBP1 Depletion in Mature Astrocytes Reveals Distinct Splicing Alterations Without Neuronal Features 95%
- Fine-tuning spatial-temporal dynamics and surface receptor expression support plasma cell-intrinsic longevity 95%
Similar papers in this journal
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 96%
- Transcriptional Control of Brain Tumour Stem Cell by a Carbohydrate Binding Protein 95%
- Hypoxia-inducible factor 1 protects neurons from Sarm1-mediated neurodegeneration 95%
Similar papers in this journal
- Brain-Engrafted Monocyte-derived Macrophages from Blood and Skull-Bone Marrow Exhibit Distinct Identities from Microglia 97%
- The Alzheimers Disease Risk Genes MS4A4A And MS4A6A Cooperate to Negatively Regulate Trem2 and Microglia states 96%
- ZBTB7A regulates MDD-specific chromatin signatures and astrocyte-mediated stress vulnerability in orbitofrontal cortex 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.