ArticleScience translational medicine2021
Targeting multiple cell death pathways extends the shelf life and preserves the function of human and mouse neutrophils for transfusion.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Bone Marrow Microenvironment Drives Mature Neutrophil to a CD83International journal of cancer · 2026Article
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Artificial Intelligence in Pharmaceutical Drug Development: Transforming Formulation and Innovation.Current drug discovery technologies · 2026Review
- Harnessing neutrophils for tissue repair and regeneration: mechanisms, biomaterial engineering strategies and translational potential.Regenerative biomaterials · 2026Review
- Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors.Signal transduction and targeted therapy · 2025Article
- Neutrophil death-more than meets the eye.Experimental hematology · 2025Review
- Role of Neutrophils in Homeostasis and Diseases.MedComm · 2025Review
- Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution.Cell · 2025Article
- FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis.Science China. Life sciences · 2025Article
- New insights into constitutive neutrophil death.Cell death discovery · 2025Review
- Effects of the pan-caspase inhibitor Q-VD-OPh on human neutrophil lifespan and function.PloS one · 2025Article
- Extracellular Vesicles Derived from Neutrophils Accelerate Bone Regeneration by Promoting Osteogenic Differentiation of BMSCs.ACS biomaterials science & engineering · 2024Article
- Neutrophils in Physiology and Pathology.Annual review of pathology · 2024Review
- Role of neutrophils in different stages of atherosclerosis.Innate immunity · 2023Review
- CAR-neutrophil mediated delivery of tumor-microenvironment responsive nanodrugs for glioblastoma chemo-immunotherapy.Nature communications · 2023Article
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- Article
- Neutrophil-mediated delivery of the combination of colistin and azithromycin for the treatment of bacterial infection.iScience · 2022Article
- Comparison of Neutrophil Function in Granulocyte Concentrates From Prednisone- and G-CSF-Treated Donors: Effect of Stimulant, Leukapheresis and Storage.Frontiers in medicine · 2022Article
- Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
Clinical outcomes from granulocyte transfusion (GTX) are disadvantaged by the short shelf life and compromised function of donor neutrophils. Spontaneous neutrophil death is heterogeneous and mediated by multiple pathways. Leveraging mechanistic knowledge and pharmacological screening, we identified a combined treatment, caspases-lysosomal membrane permeabilization-oxidant-necroptosis inhibition plus granulocyte colony-stimulating factor (CLON-G), which altered neutrophil fate by simultaneously targeting multiple cell death pathways. CLON-G prolonged human and mouse neutrophil half-life in vitro from less than 1 day to greater than 5 days. CLON-G-treated aged neutrophils had equivalent morphology and function to fresh neutrophils, with no impairment to critical effector functions including phagocytosis, bacterial killing, chemotaxis, and reactive oxygen species production. Transfusion with stored CLON-G-treated 3-day-old neutrophils enhanced host defenses, alleviated infection-induced tissue damage, and prolonged survival as effectively as transfusion with fresh neutrophils in a clinically relevant murine GTX model of neutropenia-related bacterial pneumonia and systemic candidiasis. Last, CLON-G treatment prolonged the shelf life and preserved the function of apheresis-collected human GTX products both ex vivo and in vivo in immunodeficient mice. Thus, CLON-G treatment represents an effective and applicable clinical procedure for the storage and application of neutrophils in transfusion medicine, providing a therapeutic strategy for improving GTX efficacy.
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Registered trials
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.