Chorionic villus‐derived mesenchymal stem cells induce E3 ligase TRIM72 expression and regulate cell behaviors through ubiquitination of p53 in trophoblasts

Abstract Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function.Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts.Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment.Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

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Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

Cell & Bioscience ◽

10.1186/s13578-021-00681-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yijing Chu ◽

Chengzhan Zhu ◽

Chongyu Yue ◽

Wei Peng ◽

Weiping Chen ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chorionic Villus ◽

Protein Levels ◽

Hypoxic Conditions ◽

Upstream Regulator ◽

Before And After ◽

Pathway Analyses ◽

Stat3 Signalling ◽

Proliferation And Invasion

Abstract Background Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. Several studies have revealed that human chorionic villous mesenchymal stem cells (CV-MSCs) could regulate trophoblasts function. Results To understand how human chorionic villous mesenchymal stem cells (CV-MSCs) regulate trophoblast function, we treated trophoblasts with CV-MSC supernatant under hypoxic conditions. Treatment markedly enhanced proliferation and invasion and augmented autophagy. Transcriptome and pathway analyses of trophoblasts before and after treatment revealed JAK2/STAT3 signalling as an upstream regulator. In addition, STAT3 mRNA and protein levels increased during CV-MSC treatment. Consistent with these findings, JAK2/STAT3 signalling inhibition reduced the autophagy, survival and invasion of trophoblasts, even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, STAT3 overexpression increased autophagy levels in trophoblasts; thus, it positively regulated autophagy in hypoxic trophoblasts. Human placental explants also proved our findings by showing that STAT3 was activated and that LC3B-II levels were increased by CV-MSC treatment. Conclusion In summary, our data suggest that CV-MSC-dependent JAK2/STAT3 signalling activation is a prerequisite for autophagy upregulation in trophoblasts. Graphic abstract

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Cellular Spheroids of Mesenchymal Stem Cells and Their Perspectives in Future Healthcare

Applied Sciences ◽

10.3390/app9040627 ◽

2019 ◽

Vol 9 (4) ◽

pp. 627 ◽

Cited By ~ 8

Author(s):

Hao-Wei Han ◽

Shigetaka Asano ◽

Shan-hui Hsu

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Therapeutic Potential ◽

Three Dimensional ◽

3D Cell Culture ◽

Factors Affecting ◽

Cell Behaviors ◽

Cellular Spheroids ◽

Physical And Chemical

Intrinsic cellular properties of several types of cells are dramatically altered as the culture condition shifts from two-dimensional (2D) to three-dimensional (3D) environment. Currently, several lines of evidence have demonstrated the therapeutic potential of mesenchymal stem cells (MSCs) in regenerative medicine. MSCs not only replenish the lost cells, they also promote the regeneration of impaired tissues by modulating the immune responses. Following the development of 3D cell culture, the enhanced therapeutic efficacy of spheroid-forming MSCs have been identified in several animal disease models by promoting differentiation or trophic factor secretion, as compared to planar-cultured MSCs. Due to the complicated and multifunctional applications in the medical field, MSCs are recently named as medicinal signaling cells. In this review, we summarize the predominant differences of cell–environment interactions for the MSC spheroids formed by chitosan-based substrates and other scaffold-free approaches. Furthermore, several important physical and chemical factors affecting cell behaviors in the cell spheroids are discussed. Currently, the understanding of MSCs spheroid interactions is continuously expanding. Overall, this article aims to review the broad advantages and perspectives of MSC spheroids in regenerative medicine and in future healthcare.

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Human Chorionic Villus Stem Cells May Contribute to Endogenous Factor VIII Production during Gestation

Blood ◽

10.1182/blood.v126.23.1082.1082 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1082-1082

Author(s):

Maricel G. Miguelino ◽

Priyadarsini Kumar ◽

Jerry S. Powell ◽

Aijun Wang

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Human Placenta ◽

Chorionic Villus ◽

Culture Conditions ◽

Biologically Active ◽

Early Gestation ◽

Chromogenic Assay ◽

Lineage Differentiation ◽

Coagulation Proteins

Abstract INTRODUCTION: The placenta is an organ that plays a vital role in providing nutrition, elimination of metabolic products and gas exchange for the growing fetus. Major organs that play these roles in an adult are undergoing development during gestation. The liver, a metabolic organ with a variety of endocrine and exocrine functions including the synthesis of coagulation proteins, is the major site of hematopoiesis at 11-15 weeks during gestation. Production of coagulation proteins during gestation remains unclear. We investigated the potential of very early gestation human chorionic villus mesenchymal stem cells (PMSCs) for Factor VIII (FVIII) mRNA and production of biologically active FVIII. METHODOLOGY: PMSCs were isolated from human placenta at 9-13 weeks of gestational age by tissue explant culture and characterized via flow cytometry for mesenchymal stem cell (MSC) markers. Tri-lineage differentiation of PMSCs was investigated by inducing PMSCs in different culture conditions. Polymerase chain reaction (RT-PCR) was performed on cell lysates using FVIII primers. Chromogenic assay was performed on culture medium of PMSCs and HUVECs (negative control) after 72 hours in culture. Human plasma was used as positive control. RESULTS: PMSCs isolated from preterm human placenta were plastic adherent, showed spindle-shaped morphology and demonstrated expression of MSC markers CD105, CD90, CD73, CD44, and CD29, and did not express CD184, HLA-DR or hematopoietic and endothelial markers CD45, CD34 and CD31. Tri-lineage differentiation potential into osteogenic, adipogenic and chondrogenic lineages was observed under different culture conditions. These results show multi-potency and a surface marker profile analogous to bone marrow mesenchymal stem cells (BMSCs). PCR analysis revealed FVIII mRNA expression on PMSCs and was negative on HUVECs. Chromogenic assay showed ~0.4 U/ml on PMSCs and ~0.1 U/ml in HUVECs. CONCLUSION: Here we report that early gestation PMSCs express and secrete biologically active FVIII. Further studies using different gestational ages of the placenta is needed to understand the potential contribution of chorionic villus to FVIII production during gestation. Disclosures Powell: CSL Behring: Employment.

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Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

10.21203/rs.3.rs-43803/v1 ◽

2020 ◽

Author(s):

Yijing Chu ◽

Chongyu Yue ◽

Wei Peng ◽

Weiping Chen ◽

Yan Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chorionic Villus ◽

Pcr Analysis ◽

Rna Seq ◽

Protein Levels ◽

Hypoxic Conditions ◽

Upstream Regulator ◽

Pathway Analyses ◽

Stat3 Signalling

Abstract Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function. Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts. Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment. Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

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Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo

Oxidative Medicine and Cellular Longevity ◽

10.1155/2022/2235335 ◽

2022 ◽

Vol 2022 ◽

pp. 1-13

Author(s):

Huangdi Li ◽

Jinghui Huang ◽

Yanpeng Wang ◽

Ziyuan Chen ◽

Xing Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Surface Characteristics ◽

Titanium Implants ◽

Bone Mesenchymal Stem Cells ◽

H2o2 Treatment ◽

Cell Behaviors ◽

Rat Bone

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters’ influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

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Surface modification of polymeric electrospun scaffolds via a potent and high-affinity integrin α4β1 ligand improved the adhesion, spreading and survival of human chorionic villus-derived mesenchymal stem cells: a new insight for fetal tissue engineering

Journal of Materials Chemistry B ◽

10.1039/c9tb02309g ◽

2020 ◽

Vol 8 (8) ◽

pp. 1649-1659 ◽

Cited By ~ 3

Author(s):

Dake Hao ◽

Bowen Ma ◽

Chuanchao He ◽

Ruiwu Liu ◽

Diana L. Farmer ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chorionic Villus ◽

Fetal Tissue ◽

Electrospun Scaffolds ◽

High Affinity ◽

Synthetic Biomaterial ◽

Biomaterial Scaffolds ◽

Integrin Ligand

Presenting a potent and high-affinity integrin ligand on the surface of synthetic biomaterial scaffolds improves stem cell-biomaterial interactions for fetal tissue engineering.

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MicroRNA124 and microRNA21-5p regulate migration, proliferation and differentiation of rat bone marrow mesenchymal stem cells

Bioscience Reports ◽

10.1042/bsr20193531 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Yan Liu ◽

Xiaofu Zhang ◽

Chao Gao ◽

Hang Zhang ◽

Hongtao Zhang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Neuronal Differentiation ◽

Stromal Cells ◽

Curative Effect ◽

Neurologic Diseases ◽

Cell Behaviors ◽

Proliferation And Differentiation ◽

Marrow Mesenchymal Stem Cells ◽

Non Coding Rnas

Abstract Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be a useful source of cells for the treatment of many diseases, including neurologic diseases. The curative effect of MSCs relies mostly on cell’s capacity of migration, proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles on regulating various cell behaviors. Here, we report that miRNA-124 (miR124) and miRNA-21-5p (miR21-5p) display different regulatory roles on migration, proliferation and neuron differentiation of MSCs. MiR124 was shown greatly promoting MSCs migration and neuronal differentiation. MiR21-5p could significantly enhance the proliferation and neuronal differentiation ability of MSCs. MiR124 and miR21-5p synergistically promote differentiation of MSCs into neurons. Collectively, miR124 and miR21-5p can functionally regulate cell migration, proliferation and neuronal differentiation of MSCs. Therefore, miR124 and miR21-5p may be promising tools to improve transplantation efficiency for neural injury.

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