M1 macrophage-derived exosomes transfer miR-222 to induce bone marrow mesenchymal stem cell apoptosis

This study aims to investigate whether bone marrow mesenchymal stem cell (BMSC) exosomes (BMSC-exos) affects the progression of colon cancer. Ultracentrifugation was used to extract and collect BMSC-exos which were assessed under electron microscope and by flow cytometry. The BMSCs were divided into two groups: control group treated with α-MEM basal medium and experimental group with exosomes (10 μg/ml). Exos were extracted from BMSCs and co-cultured with colon cancer cells, followed by analysis of cell viability by CCK-8 assay and GLUT3 mRNA and protein expression by RT-qPCR and Western blot. The electron microscope analysis indicated that the primary BMSCs showed a long spindle shape with a negative expression of antigen CD34 and positive antigen CD90. Importantly, exos inhibited the viability of colon cancer cells HCT116 and decreased the expression of GLUT3, suggesting that exos might increase the colon cancer cell apoptosis. In conclusion, BMSC-exos inhibit cell progression in colon cancer and might be served as a promising biomarker.

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SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

Protein & Cell ◽

10.1007/s13238-011-1097-z ◽

2011 ◽

Vol 2 (10) ◽

pp. 845-854 ◽

Cited By ~ 138

Author(s):

Xiaolei Liu ◽

Biyan Duan ◽

Zhaokang Cheng ◽

Xiaohua Jia ◽

Lina Mao ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Apoptosis ◽

Cytokine Secretion ◽

Cxcr4 Axis

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2,5‐hexanedione induces bone marrow mesenchymal stem cell apoptosis via inhibition of Akt/Bad signal pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.26602 ◽

2018 ◽

Vol 119 (4) ◽

pp. 3732-3743 ◽

Cited By ~ 6

Author(s):

Jingsong Sun ◽

Xiaoxia Shi ◽

Shuangyue Li ◽

Fengyuan Piao

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Apoptosis ◽

Signal Pathway

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Dissecting Molecular Mechanisms Underlying H2O2-induced Apoptosis of Mouse Bone Marrow Mesenchymal Stem Cell: Role of Mst1 Inhibition.

10.21203/rs.3.rs-45400/v2 ◽

2020 ◽

Author(s):

Qian Zhang ◽

Xianfeng Cheng ◽

Haizhou Zhang ◽

Tao Zhang ◽

Zhengjun Wang ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Apoptosis ◽

Caspase 3 ◽

Signal Pathway ◽

Cell Counting ◽

Ros Production ◽

Stress Injury ◽

Underlying Mechanisms

Abstract Background: Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover whether Mst1 inhibition enhanced the tolerance of BM-MSCs under H2O2 condition and the underlying mechanisms. Methods: Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H 2 O 2 . Cell viability was detected by Cell counting Kit 8 (CCK-8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H 2 O 2 -treated BM-MSC/sh-Mst1 was also measured. Results: Mst1 inhibition reduced ROS production, increased antioxidant enzyme SOD1/2, CAT, GPx expression, maintained ΔΨm, and alleviated cell apoptosis in H 2 O 2 -treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. The autophagy inhibitor, the antioxidant pathway Keap1/Nrf2, was also blocked when autophagy was inhibited by 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression. Conclusion: Mst1 inhibition mediates the cytoprotective benefit of mBM-MSCs against H 2 O 2 oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway.

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Dissecting molecular mechanisms underlying H2O2-induced apoptosis of mouse bone marrow mesenchymal stem cell: role of Mst1 inhibition

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02041-7 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Qian Zhang ◽

Xianfeng Cheng ◽

Haizhou Zhang ◽

Tao Zhang ◽

Zhengjun Wang ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Apoptosis ◽

Caspase 3 ◽

Signal Pathway ◽

Cell Counting ◽

Ros Production ◽

Stress Injury ◽

Underlying Mechanisms

Abstract Background Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover the underlying mechanisms the effect of Mst1 inhibition on the tolerance of BM-MSCs under H2O2 condition. Methods Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H2O2. Cell viability was detected by Cell Counting Kit 8 (CCK-8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus, and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H2O2-treated BM-MSC/sh-Mst1 was also measured. Results Mst1 inhibition reduced ROS production; increased antioxidant enzyme SOD1/2, CAT, and GPx expression; maintained ΔΨm; and alleviated cell apoptosis in H2O2-treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. Moreover, the antioxidant pathway Keap1/Nrf2 was also blocked when autophagy was inhibited by the autophagy inhibitor 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression. Conclusion Mst1 inhibition mediated the cytoprotective action of mBM-MSCs against H2O2-induced oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway. Graphical abstract

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Effects of bone marrow mesenchymal stem cell transplantation on tumor necrosis factor-alpha receptor 1 expression, granulosa cell apoptosis, and folliculogenesis repair in endometriosis mouse models

Veterinary World ◽

10.14202/vetworld.2021.1788-1796 ◽

2021 ◽

pp. 1788-1796

Author(s):

Sri Ratna Dwiningsih ◽

Soehartono Darmosoekarto ◽

Hendy Hendarto ◽

Erry Gumilar Dachlan ◽

Fedik Abdul Rantam ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Granulosa Cell ◽

Mouse Models ◽

Cell Apoptosis ◽

Necrosis Factor Alpha ◽

Mesenchymal Stem Cell Transplantation

Background and Aim: Endometriosis affects the ovaries and causes a decrease in the oocyte quality during endometrial receptivity. During the development of ovarian follicles, paracrine communication occurs between granulosa cells and oocytes. This study was conducted to determine the effects of bone marrow mesenchymal stem cell transplantation on tumor necrosis factor-alpha (TNF-α) receptor 1 (TNFR1) expression, granulosa cell apoptosis, and folliculogenesis in endometriosis mouse models. Materials and Methods: This study involved 42 female mice, which were divided into three groups: Healthy mice (T0), endometriosis mice without transplantation (T1), and endometriosis mice with bone marrow mesenchymal stem cell transplantation (T2). The mice were injected intraperitoneally with endometrial fragments (200 μL) to become endometriosis models. On day 15, the endometriosis models received mesenchymal stem cells. Sample collection was performed on day 29. Granulosa cell apoptosis and TNFR1 expression were examined using immunohistochemical staining, and folliculogenesis was assessed using hematoxylin and eosin staining of ovary samples. The data obtained from both examinations were statistically analyzed using Statistical Package for the Social Sciences. Results: The results showed that TNFR1 expression is significantly decreased in T2 (p<0.004). The apoptosis of granulosa cells was lower in T2 (p<0.000). The primary, secondary, and graafian follicle counts in T2 were significantly increased. Conclusion: Bone marrow mesenchymal stem cell transplantation in endometriosis mouse models can reduce TNFR1 expression and granulosa cell apoptosis and improve folliculogenesis.

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Dissecting Molecular Mechanisms Underlying H2O2-induced Apoptosis of Mouse Bone Marrow Mesenchymal Stem Cell: Role of Mst1 Inhibition.

10.21203/rs.3.rs-45400/v1 ◽

2020 ◽

Author(s):

Qian Zhang ◽

Xianfeng Cheng ◽

Haizhou Zhang ◽

Tao Zhang ◽

Zhengjun Wang ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Cell Apoptosis ◽

Caspase 3 ◽

Signal Pathway ◽

Cell Counting ◽

Ros Production ◽

Stress Injury ◽

Underlying Mechanisms

Abstract Background Bone marrow mesenchymal stem cell (BM-MSC) has been shown to treat pulmonary arterial hypertension (PAH). However, excessive reactive oxygen species (ROS) increases the apoptosis of BM-MSCs, leading to poor survival and engraft efficiency. Thus, improving the ability of BM-MSCs to scavenge ROS may considerably enhance the effectiveness of transplantation therapy. Mammalian Ste20-like kinase 1 (Mst1) is a pro-apoptotic molecule which increases ROS production. The aim of this study is to uncover whether Mst1 inhibition enhanced the tolerance of BM-MSCs under H2O2 condition and the underlying mechanisms. Methods Mst1 expression in BM-MSCs was inhibited via transfection with adenoviruses expressing a short hairpin (sh) RNA directed against Mst1 (Ad-sh-Mst1) and exposure to H2O2. Cell viability was detected by Cell counting Kit 8 (CCK‑8) assay, and cell apoptosis was analyzed by Annexin V-FITC/PI, Caspase 3 Activity Assay kits, and pro caspase 3 expression. ROS level was evaluated by the ROS probe DCFH-DA, mitochondrial membrane potential (ΔΨm) assay, SOD1/2, CAT, and GPx expression. Autophagy was assessed using transmission electron microscopy, stubRFP-sensGFP-LC3 lentivirus and autophagy-related protein expression. The autophagy/Keap1/Nrf2 signal in H2O2-treated BM-MSC/sh-Mst1 was also measured. Results Mst1 inhibition reduced ROS production, increased antioxidant enzyme SOD1/2, CAT, GPx expression, maintained ΔΨm, and alleviated cell apoptosis in H2O2-treated BM-MSCs. In addition, this phenomenon was closely correlated with the autophagy/Keap1/Nrf2 signal pathway. The autophagy inhibitor, the antioxidant pathway Keap1/Nrf2, was also blocked when autophagy was inhibited by 3-MA. However, Keap1 or Nrf2 knockout via siRNA had no effect on autophagy activation or suppression. Conclusion Mst1 inhibition mediates the cytoprotective benefit of mBM-MSCs against H2O2 oxidative stress injury. The underlying mechanisms involve autophagy activation and the Keap1/Nrf2 signal pathway.

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