Mesenchymal Stem Cell-derived Nanovesicles as a Credible Agent for Therapy of Pulmonary Hypertension

Li Hu, Jie Wang, Donghai Lin, Yueyao Shen, Huijie Huang, Yue Cao, Yan Li, Kai Li, Yanfang Yu, Youjia Yu, Chunyan Chu, Lianju Qin, Xiaojian Wang, Haifeng Zhang, David Fulton, Feng Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have been evaluated in many studies as promising therapeutic agents for pulmonary hypertension (PH). However, low yields and heterogeneity are major barriers in the translational utility of EVs for clinical studies. To address these limitations, we fabricated MSC-derived nanovesicles (MSC-NVs) by serial extrusion through filters, resulting in MSC-NVs with characteristics similar to conventional EVs but with much higher production yields. Herein, we examined the therapeutic efficacy of MSC-NVs in preclinical models of PH in vitro and in vivo. Intervention with MSC-NVs improved the core pathologies of monocrotaline-induced PH in rats. Intravenous administration of MSC-NVs resulted in significant uptake within hypertensive lungs, pulmonary artery lesions, and especially pulmonary artery smooth muscle cells (PASMCs). In vitro, MSC-NVs inhibited PDGF-induced proliferation, migration, and phenotype switching of PASMCs. miRNA-sequencing analysis of the genetic cargo of MSC-NVs revealed that miR-125b-5p and miR-100-5p are highly abundant, suggesting that they might account for the therapeutic effects of MSC-NVs in PH. Depletion of miR-125b-5p and miR- 100-5p in MSCs almost completely abolished the beneficial effects of MSC-NVs in protecting PASMCs from PDGF-stimulated changes in vitro and also diminished the protective effects of MSC-NVs in monocrotaline-induced PH in vivo. These data highlight the efficacy and advantages of MSC-NVs over MSCEVs as a promising therapeutic strategy against PH.

Original languageEnglish (US)
Pages (from-to)61-75
Number of pages15
JournalAmerican journal of respiratory cell and molecular biology
Issue number1
StatePublished - Jul 2022
Externally publishedYes


  • mesenchymal stem cells
  • miRNAs
  • nanovesicles
  • pulmonary artery smooth muscle cells
  • pulmonary hypertension

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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