Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro

Abstract Background Mesenchymal stem cells (MSCs) are emerging as an extremely promising therapeutic agent for tissue repair. However, limitations exist such as the low numbers of MSCs obtained from donors, and the poor survival and function of donor cells. Omentin-1, a new fat depot-specific secret...

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Main Authors: Li Yin, Dan Huang, Xinxin Liu, Yongshun Wang, Jingjin Liu, Fang Liu, Bo Yu
Format: Article
Language:English
Published: BMC 2017-10-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13287-017-0676-1
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spelling doaj-866fc5fb93ee4af0b29870e6ec424fe52020-11-25T00:33:39ZengBMCStem Cell Research & Therapy1757-65122017-10-018111410.1186/s13287-017-0676-1Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitroLi Yin0Dan Huang1Xinxin Liu2Yongshun Wang3Jingjin Liu4Fang Liu5Bo Yu6Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityKey Laboratories of Education Ministry for Myocardial Ischemia Mechanism, The Second Affiliated Hospital of Harbin Medical UniversityAbstract Background Mesenchymal stem cells (MSCs) are emerging as an extremely promising therapeutic agent for tissue repair. However, limitations exist such as the low numbers of MSCs obtained from donors, and the poor survival and function of donor cells. Omentin-1, a new fat depot-specific secretory adipokine, exerts proproliferation, prosurvival, and proangiogenic functions in certain cells via an Akt-dependent mechanism; however, little is known about the influence of omentin-1 on MSCs. Methods MSCs were isolated from 60–80 g donor rats. Cell proliferation was assessed with CCK-8 and EdU assay. Cell cycle, apoptosis ratio, reactive oxygen species concentration, and mitochondrial membrane potential were detected by flow cytometry. Hoechst 33342 dye was used to assess morphological changes of apoptosis. Expression levels of Akt, FoxO3a, GSK-3β, and apoptosis- and cell cycle-associated proteins were detected by Western blotting. Tube formation assay was used to test the angiogenesis role of conditioned medium from MSCs in vitro. The cytokine secretion was assessed by ELISA. Results After treatment with omentin-1 (100–800 ng/ml), MSCs displayed a higher proliferative capacity with an increasing number of cells in the S and G2 phase of the cell cycle. Moreover, omentin-1 preconditioning for 1 h could protect MSCs against H2O2-induced apoptosis in a concentration-dependent manner. Furthermore, omentin-1 pretreatment reduced the excessive reactive oxygen species. Western blots revealed that increased Bcl-2 and decreased Bax appeared in MSCs after omentin-1 incubation, which inhibited the mitochondrial apoptosis pathways with evidence showing inhibition of caspase-3 cleavage and preservation of mitochondrial membrane potential. Omentin-1 could enhance angiogenic growth factor secretion and elevate the ability of MSCs to stimulate tube formation by human umbilical vein endothelial cells (HUVECs). Furthermore, omentin-1 enhanced Akt phosphorylation; however, blockade of the PI3K/Akt pathway with an inhibitor, LY294002 (20 μM), suppressed the above beneficial effects of omentin-1. Conclusion Omentin-1 can exert beneficial effects on MSCs by promoting proliferation, inhibiting apoptosis, increasing secretion of angiogenic cytokines, and enhancing the ability for stimulating tube formation by HUVECs via the PI3K/Akt signaling pathway. Thus, omentin-1 may be considered a candidate for optimizing MSC-based cell therapy.http://link.springer.com/article/10.1186/s13287-017-0676-1Omentin-1Mesenchymal stem cellsProliferationApoptosisReactive oxygen speciesMitochondrial apoptosis pathways
collection DOAJ
language English
format Article
sources DOAJ
author Li Yin
Dan Huang
Xinxin Liu
Yongshun Wang
Jingjin Liu
Fang Liu
Bo Yu
spellingShingle Li Yin
Dan Huang
Xinxin Liu
Yongshun Wang
Jingjin Liu
Fang Liu
Bo Yu
Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
Stem Cell Research & Therapy
Omentin-1
Mesenchymal stem cells
Proliferation
Apoptosis
Reactive oxygen species
Mitochondrial apoptosis pathways
author_facet Li Yin
Dan Huang
Xinxin Liu
Yongshun Wang
Jingjin Liu
Fang Liu
Bo Yu
author_sort Li Yin
title Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
title_short Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
title_full Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
title_fullStr Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
title_full_unstemmed Omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
title_sort omentin-1 effects on mesenchymal stem cells: proliferation, apoptosis, and angiogenesis in vitro
publisher BMC
series Stem Cell Research & Therapy
issn 1757-6512
publishDate 2017-10-01
description Abstract Background Mesenchymal stem cells (MSCs) are emerging as an extremely promising therapeutic agent for tissue repair. However, limitations exist such as the low numbers of MSCs obtained from donors, and the poor survival and function of donor cells. Omentin-1, a new fat depot-specific secretory adipokine, exerts proproliferation, prosurvival, and proangiogenic functions in certain cells via an Akt-dependent mechanism; however, little is known about the influence of omentin-1 on MSCs. Methods MSCs were isolated from 60–80 g donor rats. Cell proliferation was assessed with CCK-8 and EdU assay. Cell cycle, apoptosis ratio, reactive oxygen species concentration, and mitochondrial membrane potential were detected by flow cytometry. Hoechst 33342 dye was used to assess morphological changes of apoptosis. Expression levels of Akt, FoxO3a, GSK-3β, and apoptosis- and cell cycle-associated proteins were detected by Western blotting. Tube formation assay was used to test the angiogenesis role of conditioned medium from MSCs in vitro. The cytokine secretion was assessed by ELISA. Results After treatment with omentin-1 (100–800 ng/ml), MSCs displayed a higher proliferative capacity with an increasing number of cells in the S and G2 phase of the cell cycle. Moreover, omentin-1 preconditioning for 1 h could protect MSCs against H2O2-induced apoptosis in a concentration-dependent manner. Furthermore, omentin-1 pretreatment reduced the excessive reactive oxygen species. Western blots revealed that increased Bcl-2 and decreased Bax appeared in MSCs after omentin-1 incubation, which inhibited the mitochondrial apoptosis pathways with evidence showing inhibition of caspase-3 cleavage and preservation of mitochondrial membrane potential. Omentin-1 could enhance angiogenic growth factor secretion and elevate the ability of MSCs to stimulate tube formation by human umbilical vein endothelial cells (HUVECs). Furthermore, omentin-1 enhanced Akt phosphorylation; however, blockade of the PI3K/Akt pathway with an inhibitor, LY294002 (20 μM), suppressed the above beneficial effects of omentin-1. Conclusion Omentin-1 can exert beneficial effects on MSCs by promoting proliferation, inhibiting apoptosis, increasing secretion of angiogenic cytokines, and enhancing the ability for stimulating tube formation by HUVECs via the PI3K/Akt signaling pathway. Thus, omentin-1 may be considered a candidate for optimizing MSC-based cell therapy.
topic Omentin-1
Mesenchymal stem cells
Proliferation
Apoptosis
Reactive oxygen species
Mitochondrial apoptosis pathways
url http://link.springer.com/article/10.1186/s13287-017-0676-1
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