ArticleJournal of extracellular biology2023
TDO2-augmented fibroblasts secrete EVs enriched in immunomodulatory Y-derived small RNA.
Article in Journal of extracellular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Augmentation of DNA exonuclease TREX1 in macrophages as a therapy for cardiac ischemic injury.Science translational medicine · 2025Article
- Non-coding RNA yREX3 from human extracellular vesicles exerts macrophage-mediated cardioprotection via a novel gene-methylating mechanism.European heart journal · 2024Article
- A commentary on: TDO2-augmented fibroblasts secrete EVs enriched in immunomodulatory Y-derived small RNA.Journal of extracellular biology · 2023Article
- TDO2-augmented fibroblasts secrete EVs enriched in immunomodulatory Y-derived small RNA.Journal of extracellular biology · 2023Article
Corrections and comments
- Erratum issuedCorrection to2025
Authors and funding
11 authors.
Funding
Abstract
Mounting evidence implicates extracellular vesicles (EVs) factors as mediators of cell therapy. Cardiosphere-derived cells are cardiac-derived cells with tissue reparative capacity. Activation of a downstream target of wnt/β-catenin signalling, tryptophan 2,3 dioxygenase (TDO2) renders therapeutically inert skin fibroblasts cardioprotective. Here, we investigate the mechanism by which concentrated conditioned media from TDO2-augmented fibroblasts (TDO2-CCM) exert cardioprotective effects. TDO2-CCM is cardioprotective in a mouse model of MI compared to CCM from regular fibroblasts (HDF-CCM). Transcriptomic analysis of cardiac tissue at 24 h demonstrates broad suppression of inflammatory and cell stress markers in animals given TDO2-CCM compared to HDF-CCM or vehicle. Sequencing analysis of TDO2-EV RNA demonstrated abundance of a small Y-derived small RNA dubbed 'NT4'. Purification of TDO2-EVs by size-exclusion chromatography and RNAse protection assays demonstrated that NT4 is encapsulated inside EVs. Consistently with TDO2-CCM, macrophages exposed to NT4 showed suppression of the inflammatory and cell stress mediators, particularly p21/cdkn1a. NT4-depleted TDO2-CCM resulted in diminished immunomodulatory capacity. Finally, administration of NT4 alone was cardioprotective in an acute model of myocardial infarction. Taken together, these findings elucidate the mechanism by which TDO2 augmentation mediates potency in secreted EVs through enrichment of NT4 which suppresses upstream cell stress mediators including p21/cdkn1a.
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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.