Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs) are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

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PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

BioMed Research International ◽

10.1155/2022/3697944 ◽

2022 ◽

Vol 2022 ◽

pp. 1-11

Author(s):

Wittaya Chaiwangyen ◽

Komsak Pintha ◽

Payungsak Tantipaiboonwong ◽

Piyawan Nuntaboon ◽

Orawan Khantamat ◽

...

Keyword(s):

Mirna Expression ◽

Cell Function ◽

Premature Mortality ◽

Trophoblast Cell ◽

Migration And Invasion ◽

Trophoblast Cells ◽

High Concentration ◽

Particulate Pollution ◽

Cell Functions ◽

Pollution Exposure

Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1β, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

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Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaz054 ◽

2019 ◽

Vol 25 (11) ◽

pp. 755-771 ◽

Cited By ~ 5

Author(s):

Changwon Yang ◽

Whasun Lim ◽

Junghyun Park ◽

Sunwoo Park ◽

Seungkwon You ◽

...

Keyword(s):

Mouse Model ◽

Cell Line ◽

Trophoblast Cell ◽

Migration And Invasion ◽

Human Umbilical Cord ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Exosomal Mirnas ◽

Anti Inflammatory ◽

Human Trophoblast Cells

Abstract Human umbilical cord mesenchymal stem cells (MSCs) have been reported to improve the migration and invasion of trophoblast cells; however, little is known about whether MSC-derived exosomes and exosomal miRNAs can regulate trophoblast cell properties. In this study, we investigated whether exosomal miRNAs from amniotic fluid-derived MSC (AF-MSC) could regulate the inflammatory response of the human trophoblast cell line HTR8/SVneo. We verified the anti-inflammatory effects of AF-MSCs on lipopolysaccharide (LPS)-induced inflammatory trophoblast cells and found that miR-146a-5p and miR-548e-5p in the AF-MSC–derived exosomes regulate nuclear factor κB, AKT and mitogen-activated protein kinase protein phosphorylation. Furthermore, we found that the transfection of human trophoblast cells with miR-146a-5p and miR-548e-5p inhibitors reduced trophoblast migration (P < 0.05 vs control) and the expression of proliferating cell nuclear antigen, a protein essential for cell proliferation (P < 0.01 vs control). In particular, the miR-548e-5p inhibitor induced apoptosis, while tumor necrosis factor receptor–associated factor 6, a predicted target of miR-146a-5p and miR-548e-5p, was involved in the regulation of oxidative stress in the human trophoblast cells. In a mouse model of LPS-induced preterm birth (PB), miR-146a-5p expression was found to be relatively low in the group in which the effect of AF-MSCs was insignificant. However, this study is limited in that the changes in the expression of some genes in response to AF-MSCs differ between the cell line and mouse model. Collectively, these data show that exosomal miR-146a-5p and miR-548e-5p from AF-MSCs have anti-inflammatory effects on human trophoblast cells and may be novel targets for treating inflammatory diseases and associated problems that occur during pregnancy, such as PB.

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Dimethyl Sulfoxide-Free Cryopreservation of Human Umbilical Cord Mesenchymal Stem Cells Based on Zwitterionic Betaine and Electroporation

International Journal of Molecular Sciences ◽

10.3390/ijms22147445 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7445

Author(s):

Lei Gao ◽

Qianqian Zhou ◽

Yulong Zhang ◽

Sujing Sun ◽

Liping Lv ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Dimethyl Sulfoxide ◽

Umbilical Cord ◽

Cell Function ◽

Freezing Point ◽

Pure Water ◽

Basic Research ◽

Human Umbilical Cord

The effective cryopreservation of mesenchymal stem cells (MSCs) is indispensable to the operation of basic research and clinical transplantation. The prevalent protocols for MSC cryopreservation utilize dimethyl sulfoxide (DMSO), which is easily permeable and able to protect MSCs from cryo-injuries, as a primary cryoprotectant (CPA). However, its intrinsic toxicity and adverse effects on cell function remain the bottleneck of MSC cryopreservation. In this work, we cryopreserved human umbilical cord mesenchymal stem cells (UCMSCs) using zwitterionic betaine combined with electroporation without any addition of DMSO. Betaine was characterized by excellent compatibility and cryoprotective properties to depress the freezing point of pure water and balance the cellular osmotic stress. Electroporation was introduced to achieve intracellular delivery of betaine, intending to further provide comprehensive cryoprotection on UCMSCs. Compared with DMSO cryopreservation, UCMSCs recovered from the protocol we developed maintained the normal viability and functions and reduced the level of reactive oxygen species (ROS) that are harmful to cell metabolism. Moreover, the in vivo distribution of thawed UCMSCs was consistent with that of fresh cells monitored by a bioluminescence imaging (BLI) system. This work opens a new window of opportunity for DMSO-free MSC cryopreservation using zwitterionic compounds like betaine combined with electroporation.

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The Effect of miR122 and miR185 on Hepatic Differentiation of Human Umbilical Cord Mesenchymal Stem Cells

10.21203/rs.3.rs-37954/v1 ◽

2020 ◽

Author(s):

Qun YU ◽

Sha LV ◽

Wen Jun SU ◽

Yan Feng YIN ◽

Zheng GUAN ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Fate ◽

Umbilical Cord ◽

Mrna Level ◽

Antagonistic Effect ◽

Human Umbilical Cord ◽

Hepatic Differentiation ◽

Cell Functions ◽

Hepatocyte Markers

Abstract Background: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been considered as a promising cell source in liver diseases. miRNAs have been shown to play an important role in hepatic differentiation of hUC-MSCs. The study seeks to explore whether miR122 and miR185 could affect induction of hUC-MSCs into hepatic differentiation. Methods: miR122 and miR185 stable overexpression by hUC-MSCs were firstly created, then hUC-MSCs were cultured by hepatic differentiation conditional medium. After 28 days culture in hepatic inducing conditional medium, hepatic markers expressed by these cells were detected by qRT-PCR and western-blot. The cell functions were also evaluated by PAS staining and ICG phagocytosis. Results: Our results demonstrated that at the end of 28 days, hUC-MSCs overexpressing miR122 had increasing expression of hepatocyte markers including AFP, ALB, CK18, CK19 and HNF4α in both mRNA level and protein ecpression, while in the miR185 overexpression group, hUC-MSCs showed decreasing expression of hepatocyte markers. Moreover, there was also improvement of glycogen deposits as well as ICG phagocytosis ability in the hepatic inducing miR122 overexpression cells, while in the hepatic inducing miR185 overexpression group, hUC-MSCs showed decreasing glycogen deposits and ICG phagocytosis ability. Conclusions: We thus speculate that it is possible to promote hepatic differentiation of hUC-MSCs by overexpression of miR122 and this effect may be inhibited by miR185 overexpression. It seems miR122 and miR185 have an antagonistic effect on hUC-MSCs hepatic differentiation. Overexpression of certain kind of miRNA in cells by transfection or other gene modification skills could be an effective way to modulate stem cell fate.

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