Evidence map›Paper›PMID 33577723›Full record

ArticleStem cells translational medicine2021

Development of an optimized and scalable method for isolation of umbilical cord blood-derived small extracellular vesicles for future clinical use.

Renato M S Cardoso, Silvia C Rodrigues, Claudia F Gomes, Filipe V Duarte, Maryse Romao, Ermelindo C Leal, Patricia C Freire, Ricardo Neves, Joana Simões-Correia

Abstract read
In one paragraph

Article in Stem cells translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
–field-weighted citation impact
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

29 citing papers in PubMed.

  1. Extension of the fluidics NTF-Biobank of polytraumatized patients with extracellular vesicles: improved vesicle preservation through local processing.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2026
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  20. Stem cell-mediated angiogenesis in skin tissue engineering and wound healing.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022
    Review
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

9 authors.

Renato M S CardosoExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0002-1171-2084
Silvia C RodriguesExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0001-9955-6882
Claudia F GomesExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0001-7308-1890
Filipe V DuarteExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0003-0287-0328
Maryse RomaoInstitut Curie, Paris Sciences Lettres Research University, Centre National de la Recherche Scientifique, UMR 144, Paris, France.
Ermelindo C LealCNC-Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.ORCID 0000-0003-1748-9861
Patricia C FreireExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0001-8916-9782
Ricardo NevesExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0003-2291-6610
Joana Simões-CorreiaExogenus Therapeutics, S.A, Biocant Park, Cantanhede, Portugal.ORCID 0000-0003-2623-5628

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extracellular vesicles (EV) are a promising therapeutic tool in regenerative medicine. These particles were shown to accelerate wound healing, through delivery of regenerative mediators, such as microRNAs. Herein we describe an optimized and upscalable process for the isolation of EV smaller than 200 nm (sEV), secreted by umbilical cord blood mononuclear cells (UCB-MNC) under ischemic conditions and propose quality control thresholds for the isolated vesicles, based on the thorough characterization of their protein, lipid and RNA content. Ultrafiltration and size exclusion chromatography (UF/SEC) optimized methodology proved superior to traditional ultracentrifugation (UC), regarding production time, standardization, scalability, and vesicle yield. Using UF/SEC, we were able to recover approximately 400 times more sEV per mL of media than with UC, and upscaling this process further increases EV yield by about 3-fold. UF/SEC-isolated sEV display many of the sEV/exosomes classical markers and are enriched in molecules with anti-inflammatory and regenerative capacity, such as hemopexin and miR-150. Accordingly, treatment with sEV promotes angiogenesis and extracellular matrix remodeling, in vitro. In vivo, UCB-MNC-sEV significantly accelerate skin regeneration in a mouse model of delayed wound healing. The proposed isolation protocol constitutes a significant improvement compared to UC, the gold-standard in the field. Isolated sEV maintain their regenerative properties, whereas downstream contaminants are minimized. The use of UF/SEC allows for the standardization and upscalability required for mass production of sEV to be used in a clinical setting.

Indexed as

ExosomesExtracellular VesiclesFetal BloodAnimalsBiomarkersMiceMicroRNAsBiomarkersMicroRNAsangiogenesiscell signalingcellular therapyclinical translationmicroRNAstem cellstissue regenerationumbilical cord blood

Identifiers

PMID33577723
PMCPMC8133342

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Registered trials

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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.