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Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids
The mechanisms underlying the therapeutic potential of MSCs are the focus of intense research. We studied human MSCs isolated from desquamated endometrium (eMSCs), which, as previously shown, have high regenerative potential in various disease models. The aim was to evaluate the role of secreted VEG...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695450/ https://www.ncbi.nlm.nih.gov/pubmed/36430800 http://dx.doi.org/10.3390/ijms232214324 |
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author | Kozhukharova, Irina Minkevich, Natalia Alekseenko, Larisa Domnina, Alisa Lyublinskaya, Olga |
author_facet | Kozhukharova, Irina Minkevich, Natalia Alekseenko, Larisa Domnina, Alisa Lyublinskaya, Olga |
author_sort | Kozhukharova, Irina |
collection | PubMed |
description | The mechanisms underlying the therapeutic potential of MSCs are the focus of intense research. We studied human MSCs isolated from desquamated endometrium (eMSCs), which, as previously shown, have high regenerative potential in various disease models. The aim was to evaluate the role of secreted VEGF in stimulating angiogenesis and maintaining eMSC viability and migration, which is important for improving the therapeutic properties of MSCs. We compared three eMSC cultures differing in the level of VEGF secretion: 3D spheroids, monolayer eMSCs, and monolayer eMSCs with VEGF knockdown. Spheroid eMSCs produced higher amounts of VEGF and had the strongest paracrine effect on HUVEC. eMSCs with VEGF knockdown did not stimulate angiogenesis. Monolayered eMSCs expressed VEGFR1, while spheroid eMSCs expressed both VEGFR1 and VEGFR2 receptors. The knockdown of VEGF caused a significant decrease in the viability and migration of eMSCs. eMSCs from 3D spheroids enhanced proliferation and migration in response to exogenous VEGF, in contrast to monolayered eMSCs. Our results suggest that the VEGF–VEGFR1 loop appears to be autocrine-involved in maintaining the viability of eMSCs, and VEGFR2 expression enhances their response to exogenous VEGF, so the angiogenic potential of eMSC can be up- or downregulated by intrinsic VEGF signals. |
format | Online Article Text |
id | pubmed-9695450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96954502022-11-26 Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids Kozhukharova, Irina Minkevich, Natalia Alekseenko, Larisa Domnina, Alisa Lyublinskaya, Olga Int J Mol Sci Article The mechanisms underlying the therapeutic potential of MSCs are the focus of intense research. We studied human MSCs isolated from desquamated endometrium (eMSCs), which, as previously shown, have high regenerative potential in various disease models. The aim was to evaluate the role of secreted VEGF in stimulating angiogenesis and maintaining eMSC viability and migration, which is important for improving the therapeutic properties of MSCs. We compared three eMSC cultures differing in the level of VEGF secretion: 3D spheroids, monolayer eMSCs, and monolayer eMSCs with VEGF knockdown. Spheroid eMSCs produced higher amounts of VEGF and had the strongest paracrine effect on HUVEC. eMSCs with VEGF knockdown did not stimulate angiogenesis. Monolayered eMSCs expressed VEGFR1, while spheroid eMSCs expressed both VEGFR1 and VEGFR2 receptors. The knockdown of VEGF caused a significant decrease in the viability and migration of eMSCs. eMSCs from 3D spheroids enhanced proliferation and migration in response to exogenous VEGF, in contrast to monolayered eMSCs. Our results suggest that the VEGF–VEGFR1 loop appears to be autocrine-involved in maintaining the viability of eMSCs, and VEGFR2 expression enhances their response to exogenous VEGF, so the angiogenic potential of eMSC can be up- or downregulated by intrinsic VEGF signals. MDPI 2022-11-18 /pmc/articles/PMC9695450/ /pubmed/36430800 http://dx.doi.org/10.3390/ijms232214324 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kozhukharova, Irina Minkevich, Natalia Alekseenko, Larisa Domnina, Alisa Lyublinskaya, Olga Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title | Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title_full | Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title_fullStr | Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title_full_unstemmed | Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title_short | Paracrine and Autocrine Effects of VEGF Are Enhanced in Human eMSC Spheroids |
title_sort | paracrine and autocrine effects of vegf are enhanced in human emsc spheroids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695450/ https://www.ncbi.nlm.nih.gov/pubmed/36430800 http://dx.doi.org/10.3390/ijms232214324 |
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