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. 2022 Sep-Oct;19(5):570-575.
doi: 10.21873/cgp.20341.

In Vivo Effects of Conditioned Medium from Human Uterine Cervical Stem Cells in an Ovarian Cancer Xenograft Mouse Model

Juan Sendon-Lago  1 , Samuel Seoane  1 , Fatima Saleh  2 , Lucia Garcia-Caballero  3 , Maria E Arias  4 , Noemi Eiro  5 , Manuel Macia  4 , Francisco J Vizoso  5 , Roman Perez-Fernandez  1 , Jose Schneider  6
Affiliations

In Vivo Effects of Conditioned Medium from Human Uterine Cervical Stem Cells in an Ovarian Cancer Xenograft Mouse Model

Juan Sendon-Lago et al. Cancer Genomics Proteomics. 2022 Sep-Oct.

Abstract

Background/aim: Ovarian cancer is the most lethal of all gynecological cancers, despite advances in surgical techniques and medical treatments. During the last years, therapies based on mesenchymal stem cells and particularly their secretome (conditioned medium, CM) have emerged as promising treatments for various types of tumors.

Materials and methods: In the present study, we evaluated the in vivo antitumor effect of human uterine cervical stem cell conditioned medium (hUCESC-CM) after intraperitoneal administration in an ovarian cancer mouse model.

Results: We found that intraperitoneal injection of hUCESC-CM in immunodeficient mice, injected fifty days previously with the human ovarian adenocarcinoma SKOV-3 cell line, significantly reduced abdominal tumor growth, and significantly increased overall survival, compared to control mice.

Conclusion: hUCESC-CM could be an alternative approach to intraperitoneal treatment of ovarian cancer, either administered alone and/or with conventional chemotherapy.

Keywords: Mesenchymal stem cells; conditioned medium; ovarian cancer; secretome.

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Conflict of interest statement

The Authors declare the following competing interests: Francisco J. Vizoso, Roman Perez-Fernandez, and Noemi Eiró are co-inventors of a patent (“Human uterine cervical stem cell population and uses thereof”) owned by GiStem Research, of which some authors are shareholders (JS-L, SS, NE, FV, RP-F, and JS). The founding sponsors had no role in the design of this manuscript, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1. Treatment of SKOV-3-LUC cells with hUCESC-CM reduces proliferation/cell viability. SKOV-3 cells were cultured with incomplete medium (FBS-), complete medium (FBS+), SKOV-3-CM, and hUCESCCM. After 48 h of culture, an MTT assay was carried out to evaluate cell viability. ***p<0.001.
Figure 2
Figure 2. Treatment with hUCESC-CM reduces tumor growth in an ovarian cancer mouse model. (A) Example of five mice injected intraperitoneally with SKOV-3-LUC cells at day 28. (B) Representative image of one control mouse sacrificed on day 66, showing abdominal tumors. (C) H&E staining of peritoneal tumors in controls and treated mice (days 66 and 77 after SKOV-3-LUC cells injection). Dotted lines indicate tumor length in μm. (D) H&E staining of tumors from a control (up) and a treated (down) mice at day 77. Scale bar=1 μm.
Figure 3
Figure 3. Treatment with hUCESC-CM increases overall survival in vivo in an ovarian cancer mouse model. (A) Immunohistochemistry (IHC) analysis of the Ki-67 proliferation marker in tumors of control and hUCESC-CM treated mice at day 77. Scale bar=40 μm. (B) IHC analysis of the caspase-3 apoptosis marker in tumors of control and hUCESC-CM treated mice. Scale bar=40 μm. (C) Kaplan-Meier plot of overall survival (OS) in CM-treated vs. control mice (p=0.016).
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