ArticleJournal of thrombosis and haemostasis : JTH2024
Targeting cargo to an unconventional secretory system within megakaryocytes allows the release of transgenic proteins from platelets.
Article in Journal of thrombosis and haemostasis : JTH, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
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Who cites it
6 citing papers in PubMed.
- Article
- Thiol Isomerases: Enzymatic Mechanisms, Models of Oxidation, and Antagonism by Galloylated Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.Communications biology · 2025Article
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- Looking Under the Hood at the Cytoskeletal Engine of Platelet Production.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Platelets welcome a new protein disulfide isomerase family member.Journal of thrombosis and haemostasis : JTH · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundPlatelets are essential for hemostasis and thrombosis and play vital roles during metastatic cancer progression and infection. Hallmarks of platelet function are activation, cytoskeletal rearrangements, and the degranulation of their cellular contents upon stimulation. While α-granules and dense granules are the most studied platelet secretory granules, the dense tubular system (DTS) also functions as a secretory system for vascular thiol isomerases. However, how DTS cargo is packaged and transported from megakaryocytes (MKs) to platelets is poorly understood.
objectivesTo underpin the mechanisms responsible for DTS cargo transport and leverage those for therapeutic protein packaging into platelets.
methodsA retroviral expression system combined with immunofluorescence confocal microscopy was employed to track protein DTS cargo protein disulfide isomerase fused to enhanced green fluorescent protein (eGFP-PDI) during platelet production. Murine bone marrow transplantation models were used to determine the release of therapeutic proteins from platelets.
resultsWe demonstrated that the endoplasmic reticulum retrieval motif Lys-Asp-Glu-Leu (KDEL) located at the C-terminus of protein disulfide isomerase was essential for the regular transport of eGFP-PDI-containing granules. eGFP-PDI
conclusionOur data corroborate the DTS as a noncanonical secretory system in platelets and demonstrate that in vitro-generated MKs and platelets may be used as a delivery system for transgenic proteins during cellular therapy.
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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 Socratic graph.