Bone Marrow Mesenchymal Stem Cell (BMSC) Exosomes Inhibit Angiogenesis and Enhance Autophagy Through Decreasing miR-21 in Cervical Cancer

2021 ◽  
Vol 11 (9) ◽  
pp. 1780-1784
Author(s):  
Kewei Chen ◽  
Yiqin Ouyang ◽  
Junhua Liang ◽  
Huaifang Li ◽  
Xiaowen Tong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Acridine Orange ◽  
Tube Formation ◽  
Fluorescent Staining ◽  
Insight Into

We aimed to explore the mechanism underlying the role of miR-21 derived from bone marrow mesenchymal stem cell exosomes (BMSC-exos) in cervical cancer (CC) and the relation between angiogenesis and autophagy. In this study, BMSC-exos were co-cultured with CC stem cells followed by analysis of miR-21 expression by RT-qPCR, autophagy after hunger-induced feeding by Acridine Orange fluorescent staining, angiogenesis by tube formation assay. Co-culture of BMSC-exos effectively reduced miR-21 expression in CC stem cells and enhanced autophagy as demonstrated by upregulated Beclin1 and LC3B with assembly of autophagosome (p < 0.05), but the autophagy restored later. Moreover, in the presence of BMSC-exos, CC stem cell angiogenesis was suppressed by 79%. In conclusion, BMSC-exos enhance autophagy and inhibit angiogenesis in CC through decreasing miR-21, which provides a novel insight into etiology of CC.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

scholarly journals Cytotoxic Effect of Hypoxic Environment in Mesenchymal Stem Cell

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1592
Author(s):  
Sevil Özer ◽  
H. Seda Vatansever ◽  
Feyzan Özdal-Kurt
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
Hypoxic Condition ◽  
Immunoperoxidase Technique ◽  
Cellular Functions ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.

Abstract 13: Plasminogen Is Required for Hematopoietic Stem Cell-Mediated Cardiac Repair After Myocardial Infarction

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Yanqing Gong ◽  
Jane Hoover-Plow ◽  
Ying Li
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Tissue Repair ◽  
Critical Role ◽  
Cardiac Repair ◽  
Internal Diameter ◽  
Hematopoietic Stem

Ischemic heart disease, including myocardial infarction (MI), is the primary cause of death throughout the US. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize hematopoietic progenitor and stem cells (HPSC) to improve cardiac recovery after MI. However, poor-mobilization to G-CSF is observed in 25% of patients and 10-20% of healthy donors. Therefore, a better understanding of the underlying mechanisms regulating G-CSF-induced cardiac repair may offer novel approaches for strengthening stem cell-mediated therapeutics. Our previous studies have identified an essential role of Plg in HPSC mobilization from bone marrow (BM) in response to G-CSF. Here, we investigate the role of Plg in G-CSF-stimulated cardiac repair after MI. Our data show that G-CSF significantly improves cardiac tissue repair including increasing neovascularization in the infarct area, and improving ejection fraction and LV internal diameter by echocardiogram in wild-type mice. No improvement in tissue repair and heart function by G-CSF is observed in Plg -/- mice, indicating that Plg is required for G-CSF-regulated cardiac repair after MI. To investigate whether Plg regulates HPSC recruitment to ischemia area, bone marrow transplantion (BMT) with EGFP-expressing BM cells was performed to visualize BM-derived stem cells in infarcted tissue. Our data show that G-CSF dramatically increases recruitment of GFP+ cells (by 16 fold) in WT mice but not in Plg -/- mice, suggesting that Plg is essential for HPSC recruitment from BM to the lesion sites after MI. In further studies, we investigated the role of Plg in the regulation of SDF-1/CXCR-4 axis, a major regulator for HPSC recruitment. Our results show that G-CSF significantly increases CXCR-4 expression in infarcted area in WT mice. While G-CSF-induced CXCR-4 expression is markedly decreased (80%) in Plg -/- mice, suggesting Plg may regulate CXCR-4 expression during HSPC recruitment to injured heart. Interestingly, Plg does not affect SDF-1 expression in response to G-CSF treatment. Taken together, our findings have identified a critical role of Plg in HSPC recruitment to the lesion site and subsequent tissue repair after MI. Thus, targeting Plg may offer a new therapeutic strategy to improve G-CSF-mediated cardiac repair after MI.

scholarly journals Role of geometrical cues in bone marrow-derived mesenchymal stem cell survival, growth and osteogenic differentiation

2017 ◽  
Vol 32 (7) ◽  
pp. 906-919 ◽  
Author(s):  
Dhanak Gupta ◽  
David M Grant ◽  
Kazi M Zakir Hossain ◽  
Ifty Ahmed ◽  
Virginie Sottile
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Survival ◽  
Osteogenic Differentiation ◽  
Stem Cell Survival

Differential Role for VLA-5 in Mobilization of Heamotopoieic Stem Cells Toward Peripheral Blood and Homing to Bone Marrow and Spleen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2190-2190 ◽  
Author(s):  
Pieter K. Wierenga ◽  
Ellen Weersing ◽  
Bert Dontje ◽  
Gerald de Haan ◽  
Ronald P. van Os
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Hematopoietic Stem ◽  
Late Antigen ◽  
Cell Mobilization

Abstract Adhesion molecules have been implicated in the interactions of hematopoietic stem and progenitor cells with the bone marrow extracellular matrix and stromal cells. In this study we examined the role of very late antigen-5 (VLA-5) in the process of stem cell mobilization and homing after stem cell transplantation. In normal bone marrow (BM) from CBA/H mice 79±3 % of the cells in the lineage negative fraction express VLA-5. After mobilization with cyclophosphamide/G-CSF, the number of VLA-5 expressing cells in mobilized peripheral blood cells (MPB) decreases to 36±4%. The lineage negative fraction of MPB cells migrating in vitro towards SDF-1α (M-MPB) demonstrated a further decrease to 3±1% of VLA-5 expressing cells. These data are suggestive for a downregulation of VLA-5 on hematopoietic cells during mobilization. Next, MPB cells were labelled with PKH67-GL and transplanted in lethally irradiated recipients. Three hours after transplantation an increase in VLA-5 expressing cells was observed which remained stable until 24 hours post-transplant. When MPB cells were used the percentage PKH-67GL+ Lin− VLA-5+ cells increased from 36% to 88±4%. In the case of M-MPB cells the number increased from 3% to 33±5%. Although the increase might implicate an upregulation of VLA-5, we could not exclude selective homing of VLA-5+ cells as a possible explanation. Moreover, we determined the percentage of VLA-5 expressing cells immediately after transplantation in the peripheral blood of the recipients and were not able to observe any increase in VLA-5+ cells in the first three hours post-tranpslant. Finally, we separated the MPB cells in VLA-5+ and VLA-5− cells and plated these cells out in clonogenic assays for progenitor (CFU-GM) and stem cells (CAFC-day35). It could be demonstared that 98.8±0.5% of the progenitor cells and 99.4±0.7% of the stem cells were present in the VLA-5+ fraction. Hence, VLA-5 is not downregulated during the process of mobilization and the observed increase in VLA-5 expressing cells after transplantation is indeed caused by selective homing of VLA-5+ cells. To shed more light on the role of VLA-5 in the process of homing, BM and MPB cells were treated with an antibody to VLA-5. After VLA-5 blocking of MPB cells an inhibition of 59±7% in the homing of progenitor cells in bone marrow could be found, whereas homing of these subsets in the spleen of the recipients was only inhibited by 11±4%. For BM cells an inhibition of 60±12% in the bone marrow was observed. Homing of BM cells in the spleen was not affected at all after VLA-5 blocking. Based on these data we conclude that mobilization of hematopoietic progenitor/stem cells does not coincide with a downregulation of VLA-5. The observed increase in VLA-5 expressing cells after transplantation is caused by preferential homing of VLA-5+ cells. Homing of progenitor/stem cells to the bone marrow after transplantation apparantly requires adhesion interactions that can be inhibited by blocking VLA-5 expression. Homing to the spleen seems to be independent of VLA-5 expression. These data are indicative for different adhesive pathways in the process of homing to bone marrow or spleen.

scholarly journals Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

2013 ◽  
Vol 49 (3) ◽  
pp. 235-247
Author(s):  
Hayam Abdel Meguid El Aggan ◽  
Mona Abdel Kader Salem ◽  
Nahla Mohamed Gamal Farahat ◽  
Ahmad Fathy El-Koraie ◽  
Ghaly Abd Al-Rahim Mohammed Kotb
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Stem Cell Factor ◽  
Renal Allograft ◽  
Renal Progenitor Cells ◽  
Renal Progenitor

scholarly journals Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Francesco Da Ros ◽  
Luca Persano ◽  
Dario Bizzotto ◽  
Mariagrazia Michieli ◽  
Paola Braghetta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Dependent Manner ◽  
Hematopoietic Stem

Abstract Background Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma. Methods Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry. Results Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging. Conclusion Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.

Application of Bone Marrow–Derived Mesenchymal Stem Cells for Muscle Healing After Contusion Injury in Mice

2020 ◽  
Vol 48 (5) ◽  
pp. 1226-1235 ◽  
Author(s):  
Chih-Hao Chiu ◽  
Tsan-Hsuan Chang ◽  
Shih-Sheng Chang ◽  
Gwo-Jyh Chang ◽  
Alvin Chao-Yu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Mesenchymal Stem Cell Therapy ◽  
Contusion Injury ◽  
Fast Twitch

Background: Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return to play with better function. Purpose: To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury. Study Design: Controlled laboratory study. Methods: Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 105, and 2.5 × 105 cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury. Results: The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 105 cells, 2.5 × 105 cells, 1.25 × 105 cells plus F-127, and 2.5 × 105 cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion. Conclusion: Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion. Clinical Relevance: Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.

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