Evidence map›Paper›PMID 36430812›Full record

ArticleInternational journal of molecular sciences2022

Scalable Generation of Nanovesicles from Human-Induced Pluripotent Stem Cells for Cardiac Repair.

Jonathan Lozano, Alin Rai, Jarmon G Lees, Haoyun Fang, Bethany Claridge, Shiang Y Lim, David W Greening

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 55 citations in OpenAlex.

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  17. Role of Extracellular Vesicles Produced by Stem Cells in Tissue Repair.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Jonathan LozanoBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.ORCID 0000-0002-5361-8002
Alin RaiBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Jarmon G LeesO'Brien Institute Department, St Vincent's Institute of Medical Research, Melbourne, VIC 3065, Australia.ORCID 0000-0002-9259-8657
Haoyun FangBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Bethany ClaridgeBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
Shiang Y LimO'Brien Institute Department, St Vincent's Institute of Medical Research, Melbourne, VIC 3065, Australia.ORCID 0000-0002-0442-3655
David W GreeningBaker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.ORCID 0000-0001-7516-485X
Baker Heart and Diabetes Institute · AUThe University of Melbourne · AU

Funding

National Health and Medical Research Council MRF1201805National Heart Foundation of Australia Vangard
6 · The paper itself

Abstract

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of stem cells and derived EVs for clinical utility remains a huge technical challenge. Here, we report a rapid size-based extrusion strategy to generate EV-like membranous nanovesicles (NVs) from easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical in shape and morphologically intact and readily internalised by human cardiomyocytes, primary cardiac fibroblasts, and endothelial cells. NVs captured the dynamic proteome of parental cells and include pluripotency markers (LIN28A, OCT4) and regulators of cardiac repair processes, including tissue repair (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), and extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, NVs significantly promoted tubule formation of endothelial cells (angiogenesis) (p < 0.05) and survival of cardiomyocytes exposed to low oxygen conditions (hypoxia) (p < 0.0001), as well as attenuated TGF-β mediated activation of cardiac fibroblasts (p < 0.0001). Quantitative proteome profiling of target cell proteome following NV treatments revealed upregulation of angiogenic proteins (MFGE8, MYH10, VDAC2) in endothelial cells and pro-survival proteins (CNN2, THBS1, IGF2R) in cardiomyocytes. In contrast, NVs attenuated TGF-β-driven extracellular matrix remodelling capacity in cardiac fibroblasts (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents a scalable approach to generating functional NVs for cardiac repair.

Indexed as

Induced Pluripotent Stem CellsEndothelial CellsHumansHypoxiaProteomeTransforming Growth Factor betaProteomeTransforming Growth Factor betaextracellular vesicleshuman iPSCsnanovesiclesproteomicstissue repair

Identifiers

PMID36430812
PMCPMC9696585
OpenAlexW4309737914

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.