Evidence map›Paper›PMID 34987768›Full record

ArticlePulmonary circulation

Effect of dose, dosing intervals, and hypoxic stress on the reversal of pulmonary hypertension by mesenchymal stem cell extracellular vesicles.

James R Klinger, Mandy Pereira, Michael Del Tatto, Mark S Dooner, Sicheng Wen, Peter J Quesenberry, Olin D Liang

Open access · goldAbstract read
In one paragraph

Article in Pulmonary circulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
  3. Mesenchymal stem cell therapy for pulmonary hypertension: an update.Frontiers in bioengineering and biotechnology · 2025
    Review
  4. Review
  5. Review
  6. 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

7 authors at 2 institutions in 1 country.

James R KlingerDivision of Pulmonary, Sleep and Critical Care Medicine.ORCID https://orcid.org/0000-0003-2997-5955
Mandy PereiraDivision of Hematology/Oncology, Department of Medicine, Rhode Island Hospital, Providence, USA.
Michael Del TattoDivision of Hematology/Oncology, Department of Medicine, Rhode Island Hospital, Providence, USA.
Mark S DoonerDivision of Hematology/Oncology, Department of Medicine, Rhode Island Hospital, Providence, USA.
Sicheng WenThe Alpert Medical School of Brown University, Providence, USA.
Peter J QuesenberryThe Alpert Medical School of Brown University, Providence, USA.
Olin D LiangThe Alpert Medical School of Brown University, Providence, USA.ORCID https://orcid.org/0000-0002-2266-6722
Providence College · USBrown University · US

Funding

Stem Cells and AgingP20GM119943 · NIGMS · RHODE ISLAND HOSPITAL · PI QUESENBERRY, PETER J. · 2017 to 2021
$10.6M
TYORISINE PHOSPHATASE SHP2 IN HEMATOPOIETIC STEM CELL PROPERTY MAINTENANCEP20RR025179 · NCRR · RHODE ISLAND HOSPITAL · PI ALIOTTA, JASON M · 2009 to 2011
$6.4M
NCRR NIH HHS P20 RR025179NIGMS NIH HHS P20 GM119943
6 · The paper itself

Abstract

rationaleMesenchymal stem cell extracellular vesicles (MSC EVs) reverse pulmonary hypertension, but little information is available regarding what dose is effective and how often it needs to be given. This study examined the effects of dose reduction and use of longer dosing intervals and the effect of hypoxic stress of MSC prior to EV collection.

methodsAdult male rats with pulmonary hypertension induced by Sugen 5416 and three weeks of hypoxia (SuHx-pulmonary hypertension) were injected with MSC EV or phosphate buffered saline the day of removal from hypoxia using one of the following protocols: (1) Once daily for three days at doses of 0.2, 1, 5, 20, and 100 µg/kg, (2) Once weekly (100 µg/kg) for five weeks, (3) Once every other week (100 µg/kg) for 10 weeks, (4) Once daily (20 µg/kg) for three days using EV obtained from MSC exposed to 48 h of hypoxia (HxEV) or MSC kept in normoxic conditions (NxEV). MAIN

resultsMSC EV reversed increases in right ventricular systolic pressure (RVSP), right ventricular to left ventricle + septum weight (RV/LV+S), and muscularization index of pulmonary vessels ≤50 µm when given at doses of 20 or 100 μg/kg. RVSP, RV/LV+S, and muscularization index were significantly higher in SuHx-pulmonary hypertension rats treated once weekly with phosphate buffered saline for five weeks or every other week for 10 weeks than in normoxic controls, but not significantly increased in SuHx-pulmonary hypertension rats given MSC EV. Both NxEV and HxEV significantly reduced RVSP, RV/LV+S, and muscularization index, but no differences were seen between treatment groups.

conclusionsMSC EV are effective at reversing SuHx-pulmonary hypertension when given at lower doses and longer dosing intervals than previously reported. Hypoxic stress does not enhance the efficacy of MSC EV at reversing pulmonary hypertension. These findings support the feasibility of MSC EV as a long-term treatment for pulmonary hypertension.

Indexed as

exosomespulmonary vascular remodelingright ventricular hypertrophy

Identifiers

PMID34987768
PMCPMC8723172
OpenAlexW3196718260

What OpenQuestion holds

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LicenceCC BY-NC
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.