scholarly journals Increased Differentiation Capacity of Bone Marrow-Derived Mesenchymal Stem Cells in Aquaporin-5 Deficiency

2012 ◽  
Vol 21 (13) ◽  
pp. 2495-2507 ◽  
Author(s):  
Fei Yi ◽  
Muhammad Khan ◽  
Hongwen Gao ◽  
Feng Hao ◽  
Meiyan Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Aquaporin 5 ◽  
Differentiation Capacity

scholarly journals Effects of Severe Hypoxia on Bone Marrow Mesenchymal Stem Cells Differentiation Potential

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Cicione ◽  
Emma Muiños-López ◽  
Tamara Hermida-Gómez ◽  
Isaac Fuentes-Boquete ◽  
Silvia Díaz-Prado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Control Point ◽  
Severe Hypoxia ◽  
Marker Genes ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Hypoxic Conditions

Background. The interests in mesenchymal stem cells (MSCs) and their application in cell therapy have resulted in a better understanding of the basic biology of these cells. Recently hypoxia has been indicated as crucial for complete chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation capacity under normoxic and severe hypoxic culture conditions.Methods. MSCs were characterized by flow cytometry and differentiated towards adipocytes, osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The differentiations were confirmed comparing each treated point with a control point made of cells grown in DMEM and fetal bovine serum (FBS).Results. BM-MSCs from the donors displayed only few phenotypical differences in surface antigens expressions. Analyzing marker genes expression levels of the treated cells compared to their control point for each lineage showed a good differentiation in normoxic conditions and the absence of this differentiation capacity in severe hypoxic cultures.Conclusions. In our experimental conditions, severe hypoxia affects thein vitrodifferentiation potential of BM-MSCs. Adipogenic, osteogenic, and chondrogenic differentiations are absent in severe hypoxic conditions. Our work underlines that severe hypoxia slows cell differentiation by means of molecular mechanisms since a decrease in the expression of adipocyte-, osteoblast-, and chondrocyte-specific genes was observed.

Mechanism of miR-506 Targeting Autophagy and Apoptosis-Associated Gene Beclin1 to Promote Bone Marrow Mesenchymal Stem Cells (BMSCs) Differentiation and Metastasis to Breast Cancer

2021 ◽  
Vol 11 (12) ◽  
pp. 2502-2506
Author(s):  
Qiumei Liu ◽  
Yanyan Wu ◽  
Jian Ye
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Differentiation Capacity ◽  
Marrow Mesenchymal Stem Cells ◽  
Metastasis To Breast

This study investigates miR-506 targeting the autophagy and apoptosis-related gene Beclin1 and analyzes the mechanism of its effect on bone marrow mesenchymal stem cells (BMSCs) differentiation and metastasis to breast cancer. Detection of miRNA-506 expression in BMSCs and breast cancer cells was done by Real-time PCR. A luciferase reporter system analyzed the targeting relationship between Beclin1 and miR-506. miR-NC group, BMSCs induction group, siRNA-NC group, and siRNA-Beclin1 group was set to measure Beclin1 expression, cell differentiation and migration by transwell assay, cell viability by MTT assay, proliferation by EdU staining and apoptosis and cycle by flow cell assay. miRNA-506 showed a high expression in breast cancer cells and low expression in BMSCs. miRNA-506 mimics significantly promote breast cancer cell proliferation which was inhibited by miRNA-506 inhibitors. The expression of Beclin1mRNA was significantly higher and miR-506 was lower in breast cancer cells. BMSCs induction significantly downregulated Beclin1 expression, increased miR-506 expression, and promoted cell invasive differentiation and metastatic capacity. In conclusion, elevated miR-506 expression was associated with decreased Beclin1 expression and increased metastatic differentiation capacity of breast cancer cells, which could effectively increase differentiation capacity and metastatic differentiation after induction by BMSCs.

Bisphenol A alters the self-renewal and differentiation capacity of human bone-marrow-derived mesenchymal stem cells

2016 ◽  
Vol 4 (1) ◽  
pp. e1200344 ◽  
Author(s):  
Amy L. Strong ◽  
David F. B. Miller ◽  
Aaron M. Buechlein ◽  
Fang Fang ◽  
Julie Glowacki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bisphenol A ◽  
The Self ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Self Renewal ◽  
Differentiation Capacity

scholarly journals Osteogenic/Adipogenic Imbalance in Bone Marrow Nestin+ mesenchymal Stem Cells in Patients with Chronic Graft-Versus-Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5007-5007
Author(s):  
Hanzhou Qi ◽  
Haiyan Zhang ◽  
Kaibo Yang ◽  
Yanqiu Chen ◽  
Hua Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Graft Versus Host Disease ◽  
Adipogenic Differentiation ◽  
Bone Marrow Niche ◽  
Host Disease ◽  
Differentiation Capacity ◽  
Relative Expression ◽  
Graft Versus Host

Background: Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The roles of bone marrow niche in cGVHD pathogenesis have gained increasing attention in recent years. Nestin+ mesenchymal stem cells (MSCs) is an important component of bone marrow niche. However, the potential implication of Nestin+ MSCs in the pathophysiology of cGVHD has not been completely clarified. Methods: A total of 68 patients with hematologic malignancies who underwent allo-HSCT at Nanfang Hospital between April 2016 and October 2018 were enrolled in this experimental study. We analyzed expanded Nestin+ MSCs from patients with cGVHD and compared them with patients without cGVHD. The diagnosis and grade of cGVHD was made at the time of sample collection according to National Institutes of Health criteria (Howard M.S. et. al. BBMT 2015). The results were compared using one-way ANOVA and unpaired two-tailed Student t-test. Statistical significance was defined as P value of <.05. Result: The Nestin+ MSCs from both groups showed similar morphology, immunophenotype, proliferation, and apoptosis. However, the adipogenic differentiation capacity of Nestin+ MSCs in patients with cGVHD was significantly reduced compared with patients without cGVHD (relative expression of PPARγ 2.22±0.27, and 6.82±0.87, respectively, P<0.05). The osteogenic differentiation capacity was significantly increased in patients with cGVHD (relative expression of RUNX2 3.84±0.38, and 1.95±0.52, respectively, P<0.05)(Figure 1A,B). These abnormal differentiations were more significant in patients with moderate/severe cGVHD. Furthermore, β-catenin phosphorylation decreased and nuclear β-catenin increased in the Nestin+ MSCs of cGVHD patients(Figure 1 C). Conclusion: These results demonstrate that Nestin+ MSCs from cGVHD patients had abnormal differentiation characterized by decreased adipogenic differentiation capacity and enhanced osteogenic capacity. The reduction of phosphorylation of β-catenin play an important role in these abnormal differentiations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Low-Intensity Pulsed Ultrasound Modulates RhoA/ROCK Signaling of Rat Mandibular Bone Marrow Mesenchymal Stem Cells to Rescue Their Damaged Cytoskeletal Organization and Cell Biological Function Induced by Radiation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rong Zhang ◽  
Zhaoling Wang ◽  
Guoxiong Zhu ◽  
Gaoyi Wu ◽  
Qingyuan Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
Osteogenic Differentiation ◽  
Pulsed Ultrasound ◽  
Differentiation Capacity ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Marrow Mesenchymal Stem Cells

Osteoradionecrosis of the jaw (ORNJ) is an infrequent yet potentially devastating complication of head and neck radiation therapy. Low-intensity pulsed ultrasound (LIPUS) has been widely accepted as a promising method for the successful management of ORNJ, but the mechanism remains unclear. In this study, the effects of LIPUS on cytoskeletal reorganization, cell viability, and osteogenic differentiation capacity of rat mandible-derived bone marrow mesenchymal stem cells (M-BMMSCs) induced by radiation were determined by immunofluorescence staining, CCK-8 cell proliferation assay, quantification of alkaline phosphatase (ALP) activity, alizarin red staining, and real-time RT-PCR, respectively. Moreover, the involvement of the RhoA/ROCK signaling pathway underlying this process was investigated via western blot analysis. We found that radiation induced significant damage to the cytoskeleton, cell viability, and osteogenic differentiation capacity of M-BMMSCs and downregulated their expression of RhoA, ROCK, and vinculin while increasing FAK expression. LIPUS treatment effectively rescued the disordered cytoskeleton and redistributed vinculin. Furthermore, the cell viability and osteogenic differentiation capacity were also significantly recovered. More importantly, it could reverse the aberrant expression of the key molecules induced by radiation. Inhibition of RhoA/ROCK signaling remarkably aggravated the inhibitory effect of radiation and attenuated the therapeutic effect of LIPUS. In the light of these findings, the RhoA/ROCK signaling pathway might be a promising target for modifying the therapeutic effect of LIPUS on osteoradionecrosis.

scholarly journals Minimally Manipulative Method for the Expansion of Human Bone Marrow Mesenchymal Stem Cells to Treat Osseous Defects

2019 ◽  
Vol 20 (3) ◽  
pp. 612 ◽  
Author(s):  
Logan Lawrence ◽  
Andrew Cottrill ◽  
Amrita Valluri ◽  
Gaetano Marenzi ◽  
Krista Denning ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancellous Bone ◽  
Mesenchymal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Clinical Practices ◽  
Differentiation Capacity ◽  
Hormonal Modulation

Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant osteogenic protocol for collection and expansion of autologous stem cells to be used at Marshall University for re-implantation and repair of maxillofacial and orthopedic conditions. Human bone marrow (hBM) samples were collected from patients undergoing intramedullary nail fixation for closed femoral fractures. hBM mesenchymal cells were expanded by growing them first in Petri dishes for two weeks, followed by a week of culture using Perfecta 3D Hanging Drop Plates®. Various scaffold materials were tested and analyzed for cellular integration, vitality, and differentiation capacity of harvested hBM-MSCs including: 60/40 blend of hydroxyapatite biomatrix; Acellular bone composite discs; Allowash®, cancellous bone cubes; PLGA (poly lactic-co-glycolic acid); and Woven chitin derived fiber. We found that the 3D spheroid culture allowed production of hBM mesenchymal cells that retained osteoblast differentiation capacity over a monolayer culture of hBM-MSCs without the need to use chemical or hormonal modulation. We also observed that hydroxyapatite and Allowash cancellous bone scaffolds allowed better cell integration and viability properties as compared to other materials tested in this study. In conclusion, the multimodal culture methodology we developed creates actively differentiating stem-cell spheroids that can then be readily utilized in clinical practices to improve the regeneration of tissues of the head and the body.

scholarly journals Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhenhua Liu ◽  
Peng Wang ◽  
Shuizhong Cen ◽  
Liangbin Gao ◽  
Zhongyu Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Ankylosing Spondylitis ◽  
Signaling Pathway ◽  
Adipogenic Differentiation ◽  
Marrow Fat ◽  
Differentiation Capacity ◽  
Bone Marrow Fat ◽  
Healthy Donors

Objective. To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. Methods. MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-γ, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. Protein levels of adipogenic markers and signaling pathway-related molecules were assessed via Western blotting. Levels of bone morphogenetic proteins 4, 6, 7, and 9 were determined using enzyme-linked immunosorbent assays. Lentiviruses encoding short hairpin RNAs (shRNAs) were constructed to reverse abnormal bone morphogenetic protein receptor 1A (BMPR1A) expression and evaluate its role in abnormal ASMSC adipogenic differentiation. Bone marrow fat content was assessed using hematoxylin and eosin (HE) staining. BMPR1A expression in bone marrow MSCs was measured using immunofluorescence staining. Results. ASMSCs exhibited a greater adipogenic differentiation capacity than HDMSCs. During adipogenesis, ASMSCs expressed BMPR1A at higher levels, which activated the BMP-pSmad1/5/8 signaling pathway and increased adipogenesis. BMPR1A silencing using an shRNA eliminated the difference in adipogenic differentiation between HDMSCs and ASMSCs. Moreover, HE and immunofluorescence staining showed higher bone marrow fat content and BMPR1A expression in patients with AS than in healthy donors. Conclusion. Increased BMPR1A expression induces abnormal ASMSC adipogenic differentiation, potentially contributing to fat metaplasia and thus new bone formation in patients with AS.

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