ArticleNature medicine2022
Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain.
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 82 citations in OpenAlex.
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- Hematopoietic Stem-Cell Gene Therapy for Cystinosis.The New England journal of medicine · 2026Trial
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- Characterization of hematopoietic stem cell-derived microglia-like cells in nonhuman primates.Blood advances · 2026Article
- Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease.Nature communications · 2026Article
- Microglial clonal dynamics and the impact of clonal hematopoiesis in autologously transplanted rhesus macaques.Cell reports · 2026Article
- CSF1R-related leukoencephalopathy: experimental models and potential for treatment.Disease models & mechanisms · 2026Review
- Promoting donor microglial replacement through augmented conditioning or radiation sensitivity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Brain-engrafted monocyte-derived macrophages from blood and skull-bone marrow exhibit distinct properties.Neuron · 2026Article
- Pretreatment blood NfL indicates response to cellular therapies in cerebral adrenoleukodystrophy.Communications medicine · 2026Article
- Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy.Science (New York, N.Y.) · 2026Article
- Microglia replacement by peripheral delivery of CSF1R inhibitor-resistant hematopoietic cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Autologous haematopoietic stem cell transplantation affects long-term progression independent of relapse activity in aggressive multiple sclerosis: a comparative matched study.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Article
- Chimeric enzymes enhance treatment potential for globoid cell leukodystrophy through hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Neonatal microglia replacement in mice modulates seizure severity in adulthood.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Microenvironmental conditions and serum availability alter primary human macrophage NF-κB inflammatory response and function.Journal of leukocyte biology · 2025Article
- Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1Immunity · 2025Article
- Earlier onset of chemotherapy-induced neuropathic pain in females by ICAM-1-mediated accumulation of perivascular macrophages.Science advances · 2025Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy used for pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, with the engraftment mechanism still undefined. Here we show that HSCT chemotherapy broadly disrupts mouse brain regenerative populations, including a permanent loss of adult neurogenesis. Microglial density was halved, causing microglial process expansion, coinciding with indicators of broad senescence. Although microglia expressed cell proliferation markers, they underwent cell cycle arrest in S phase with a majority expressing the senescence and antiapoptotic marker p21. In vivo single-cell tracking of microglia after recovery from chemical depletion showed loss of their regenerative capacity, subsequently replaced with donor macrophages. We propose that HSCT chemotherapy causes microglial senescence with a gradual decrease to a critical microglial density, providing a permissive niche for peripheral macrophage engraftment of the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.