Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma

Leonie Rosenberger; Marcelo Ezquer; Fernando Lillo-Vera; Paulina L. Pedraza; María Ignacia Ortúzar; Paz L. González; Aliosha I. Figueroa-Valdés; Jimena Cuenca; Fernando Ezquer; Maroun Khoury; Francisca Alcayaga-Miranda

doi:10.1038/s41598-018-36855-6

Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma

Leonie Rosenberger
, Marcelo Ezquer
, Fernando Lillo-Vera
, Paulina L. Pedraza
, María Ignacia Ortúzar
, Paz L. González
, Aliosha I. Figueroa-Valdés
, Jimena Cuenca
, Fernando Ezquer
, Maroun Khoury
, Francisca Alcayaga-Miranda^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

123 Scopus citations

Abstract

Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.

Original language	English
Article number	663
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-36855-6
State	Published - 1 Dec 2019

Bibliographical note

Funding Information:
We acknowledge the technical support and assistance of all the personnel of the Animal Facility of the Universidad del Desarrollo-Clínica Alemana. Also to Rafael Tapia for his help using BioNOC IIbased cell culture and to the Cells for Cells GMP facility for UCMSCs. We thank Fernando Figueroa for critical revision of the manuscript. This work was funded in part by CMR-UDD and Cells for Cells.

Publisher Copyright:
© 2019, The Author(s).

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10.1038/s41598-018-36855-6

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title = "Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma",

abstract = "Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.",

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AU - Ortúzar, María Ignacia

AU - González, Paz L.

AU - Figueroa-Valdés, Aliosha I.

AU - Cuenca, Jimena

AU - Ezquer, Fernando

AU - Khoury, Maroun

AU - Alcayaga-Miranda, Francisca

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PY - 2019/12/1

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N2 - Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.

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Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma

Abstract

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