ArticleCell stem cell2023
Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19.
Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Rethinking non-human primate models for emerging viral infections after COVID-19.Laboratory animal research · 2026Review
- Integrin inhibition facilitates fibrocartilaginous transformation in connective tissue in osteoarthritis.Science advances · 2026Article
- Human organoids and organ-on-chip systems for AI-guided therapeutic discovery against emerging and re-emerging infections.Frontiers in pharmacology · 2026Review
- Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids.Cell reports. Medicine · 2025Article
- Article
- CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection.Scientific reports · 2025Article
- High-throughput differentiation of human blood vessel organoids reveals overlapping and distinct functions of the cerebral cavernous malformation proteins.Angiogenesis · 2025Article
- A skin organoid-based infection platform identifies an inhibitor specific for HFMD.Nature communications · 2025Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Biological basis of critical illness subclasses: from the bedside to the bench and back again.Critical care (London, England) · 2024Review
- SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids.Scientific reports · 2024Article
- Article
- Advances in the differentiation of pluripotent stem cells into vascular cells.World journal of stem cells · 2024Review
- Emerging role of complement in COVID-19 and other respiratory virus diseases.Cellular and molecular life sciences : CMLS · 2024Review
- The new era of cardiovascular research: revolutionizing cardiovascular research with 3D models in a dish.Medical review (2021) · 2024Review
- Role of complement factor D in cardiovascular and metabolic diseases.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
35 authors at 10 institutions in 2 countries.
Funding
Abstract
COVID-19 is linked to endotheliopathy and coagulopathy, which can result in multi-organ failure. The mechanisms causing endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain elusive. Here, we developed an infection-competent human vascular organoid from pluripotent stem cells for modeling endotheliopathy. Longitudinal serum proteome analysis identified aberrant complement signature in critically ill patients driven by the amplification cycle regulated by complement factor B and D (CFD). This deviant complement pattern initiates endothelial damage, neutrophil activation, and thrombosis specific to organoid-derived human blood vessels, as verified through intravital imaging. We examined a new long-acting, pH-sensitive (acid-switched) antibody targeting CFD. In both human and macaque COVID-19 models, this long-acting anti-CFD monoclonal antibody mitigated abnormal complement activation, protected endothelial cells, and curtailed the innate immune response post-viral exposure. Collectively, our findings suggest that the complement alternative pathway exacerbates endothelial injury and inflammation. This underscores the potential of CFD-targeted therapeutics against severe viral-induced inflammathrombotic outcomes.
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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.