Evidence map›Paper›PMID 30341012›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018

Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity.

Reka Agnes Haraszti, Rachael Miller, Matteo Stoppato, Yves Y Sere, Andrew Coles, Marie-Cecile Didiot, Rachel Wollacott, Ellen Sapp, Michelle L Dubuke, Xuni Li and 5 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04753476 (The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients), which is not on this map. Cited by 341 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
341citing papers in PubMed, 2 pooled it
–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.

NCT04753476 phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

The Effect of Secretome of Hypoxia-Mesenchymal Stem Cells in Improving Survival of Severe Covid-19 Patients

TypeinterventionalSponsorStem Cell and Cancer Research IndonesiaRan2020 to 2022Enrolled48ConditionsCovid-19, Cytokine StormArmsInjection of Secretome-MSCs, Standard treatment of Covid-19
3 · Its place in the literature

Who cites it

341 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  5. Natural Product-Derived Vesicles in Nanotherapeutics.Journal of extracellular vesicles · 2026
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281 more citing papers are in PubMed but not listed here.

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

15 authors.

Reka Agnes HarasztiRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Rachael MillerDepartment of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Matteo StoppatoMassBiologics, Boston, MA, USA.
Yves Y SereMassBiologics, Boston, MA, USA.
Andrew ColesRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Marie-Cecile DidiotRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
Rachel WollacottMassBiologics, Boston, MA, USA.
Ellen SappMass General Institute for Neurodegenerative Disease, Boston, MA, USA.
Michelle L DubukeMass Spectrometry Facility, University of Massachusetts Medical School, Shrewsbury, MA, USA.
Xuni LiMass Spectrometry Facility, University of Massachusetts Medical School, Shrewsbury, MA, USA.
Scott A ShafferMass Spectrometry Facility, University of Massachusetts Medical School, Shrewsbury, MA, USA.
Marian DiFigliaMass General Institute for Neurodegenerative Disease, Boston, MA, USA.
Yang WangMassBiologics, Boston, MA, USA.
Neil AroninDepartment of Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: neil.aronin@umassmed.edu.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: anastasia.khvorova@umassmed.edu.

Funding

University of Massachusetts Center for Clinical and Translational ScienceUL1TR000161 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUZURIAGA, KATHERINE F · 2012 to 2015
$11.0M
Exosome based therapeutics in Huntington's diseaseUH3TR000888 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL, KHVOROVA, ANASTASIA · 2015 to 2017
$3.0M
Exosome based therapeutics in Huntington's diseaseUH2TR000888 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ARONIN, NEIL · 2013 to 2014
$1.1M
Mid-Scale RNA Synthesis, Purification and Quality Control SystemS10OD020012 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA · 2015 to 2015
$563k
NCATS NIH HHS UH2 TR000888NCATS NIH HHS UH3 TR000888NCATS NIH HHS UL1 TR000161NIH HHS S10 OD020012
6 · The paper itself

Abstract

Exosomes can deliver therapeutic RNAs to neurons. The composition and the safety profile of exosomes depend on the type of the exosome-producing cell. Mesenchymal stem cells are considered to be an attractive cell type for therapeutic exosome production. However, scalable methods to isolate and manufacture exosomes from mesenchymal stem cells are lacking, a limitation to the clinical translation of exosome technology. We evaluate mesenchymal stem cells from different sources and find that umbilical cord-derived mesenchymal stem cells produce the highest exosome yield. To optimize exosome production, we cultivate umbilical cord-derived mesenchymal stem cells in scalable microcarrier-based three-dimensional (3D) cultures. In combination with the conventional differential ultracentrifugation, 3D culture yields 20-fold more exosomes (3D-UC-exosomes) than two-dimensional cultures (2D-UC-exosomes). Tangential flow filtration (TFF) in combination with 3D mesenchymal stem cell cultures further improves the yield of exosomes (3D-TFF-exosomes) 7-fold over 3D-UC-exosomes. 3D-TFF-exosomes are seven times more potent in small interfering RNA (siRNA) transfer to neurons compared with 2D-UC-exosomes. Microcarrier-based 3D culture and TFF allow scalable production of biologically active exosomes from mesenchymal stem cells. These findings lift a major roadblock for the clinical utility of mesenchymal stem cell exosomes.

Indexed as

AnimalsCell Culture TechniquesCell DifferentiationCells, CulturedExosomesFemaleGene SilencingMesenchymal Stem CellsMiceNeuronsProteomeRNA, Small InterferingSpheroids, CellularUmbilical CordProteomeRNA, Small Interferingexosomesmesenchymal stem celltangential flow filtration

Identifiers

PMID30341012
PMCPMC6277553

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.