Research progress on malignant differentiation potential and mechanism of bone marrow mesenchymal stem cells

2021 ◽  
Author(s):  
Haolong Zhang ◽  
Xiao Zhang ◽  
Haoling Zhang ◽  
Rongqun Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Research Progress ◽  
Differentiation Potential ◽  
Marrow Mesenchymal Stem Cells

Differential Expression of MicroRNA-3148 in Patients with Osteoporosis and Its Impacts on the Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Vol 11 (5) ◽  
pp. 957-962
Author(s):  
Ainiwaerjiang Damaola ◽  
Maerdan Aierken ◽  
Mieralimu Muertizha ◽  
Abudouaini Abudoureheman ◽  
Haishan Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Serum Samples ◽  
Alizarin Red ◽  
Differentiation Potential ◽  
Qrt Pcr ◽  
Marrow Mesenchymal Stem Cells ◽  
Rat Bone

We aimed to explore the effects of rat bone marrow mesenchymal stem cells (BMSCs) on osteogenic differentiation via analyzing miR-3148 expression in patients with osteoporosis. Realtime quantitative PCR was conducted for assessing microRNA-3148 expression. BMSCs from SD rats were transfected with microRNA-3148 mimics and microRNA-3148 inhibitor via liposomal trans-fection method utilizing Lipo2000, followed by analysis of microRNA-3148 level. After 10-days of osteogenic differentiation induction, alkaline phosphatase (ALP) staining and alizarin red (ARS) staining were done to investigate the osteogenic differentiation potential. Simultaneously, qRT-PCR measured the expression of osteogenesis marker genes (BMP and Runx2) in each group. qRT-PCR analysis revealed a high expression of miR-3148 in the bone tissue and the serum samples from patients with osteoporosis in comparison with healthy individuals. In addition, miRNA-3148 mimics could retard the osteogenic differentiation of BMSCs, while microRNA-3148 inhibitor could prompt the procedure. MicroRNA-3148 was highly expressed in the skeletal tissues and the serum samples from patients with osteoporosis and it could restrain the differentiation of BMSCs into osteoblasts, suggesting that it might be a novel therapeutic target for treating osteoporosis.

scholarly journals Bone Marrow Mesenchymal Stem Cells from Acute Myelogenous Leukemia Patients Demonstrate Adipogenic Differentiation Propensity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5064-5064
Author(s):  
Mitra Azadniv ◽  
Jason R. Myers ◽  
Helene McMurray ◽  
John M. Ashton ◽  
Naxin Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Pathway Analysis ◽  
Adipogenic Differentiation ◽  
Myelogenous Leukemia ◽  
Normal Donor ◽  
Differentiation Potential ◽  
Airway Pathology ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) constitute one of the important cellular components of the hematopoietic microenvironmental niche. These cells are capable of differentiation into osteoprogenitors which comprise part of the endosteal niche. In vivo studies have shown that depletion of BMSCs resulted in reduction of hematopoietic stem cell content, and there is direct in vitro evidence that BMSCs are able to support both normal and leukemia progenitor cell proliferation and survival and contribute to leukemia cell resistance to cytotoxic therapies. Whether BMSCs from leukemia marrow differ from normal counterparts and how they contribute to and are influenced by the leukemia environmental niche are still incompletely understood. In this work we sought to compare normal and AML-derived BMSCs and to define the propensity of BMSCs from leukemia patients for osteogenic or adipogenic differentiation. Methods: BMSCs were isolated from marrow aspirates of normal donor and AML patients using standard methodologies. Donors were age-matched to the leukemia patients to the extent possible in each comparative experiment. Such cells met the definition of MSCs in that they were adherent and expressed CD73, CD90, CD44, CD117 and CD105 and had osteoblastic and adipogenic differentiation capabilities. All comparisons were done at comparable passage number between samples. Results: BMSCs from AML donors demonstrated irregular vs. spindle shaped morphology as compared with BMSCs from younger donors <50 years of age but similar morphology to those grown from older donors. AML derived BMSCs were larger and had slower growth rate as assessed by longer passage times during lower passages (41 vs. 21 days). Cell surface expression markers were similar between normal and AML. CFU-F outgrowth was less from AML as compared to normal BMSC, and no difference in osteogenic differentiation was noted by Alizarin Red S measurement. On the other hand, lipid droplet formation measured by Oil Red O during adipogenic differentiation induction was greater in the AML BMSCs as compared with age matched controls, suggesting increased adipogenic differentiation potential. To determine if we could detect a gene signature difference between AML and normal BMSCs which would predict adipogenic propensity, RNA-Seq analysis was performed on AML and normal donor specimens(n=3 in each group), all from subjects >50 years of age using CuffDiff (v2.0.2). This identified 88 genes differentially expressed between the two groups. A heat map was generated using Euclidean distance hierarchical clustering of gene expression values from individual samples. This readily grouped AML vs. normal samples. Pathway analysis using Ingenuity Pathway Analysis (IPA) predicted dysregulation of four canonical pathways in AML-BMSCs as compared to normal BMSCs. These included 1) Role of tissue factor in cancer, 2) Airway pathology in COPD, 3) Oleate biosynthesis, and 4) Adipogenesis. The last two pathways are consistent with the biological observation of enhanced adipogenesis in AML-derived BMSCs. IPA analysis proposed a model of altered adipogenic differentiation in AML-BMSCs attributable to lower expression of two key regulatory genes, SOX9 and EGR2. Reduced expression of SOX9 and EGR2 in AML BMSCs as compared to normal BMSCs was validated by qRT-PCR and western blot analysis. SOX9 is reported to contribute to the commitment of MSCs to adipogenic phenotype through negative influence on expression of key transcription factors in adipogenesis, and ERG2 downregulation is required in some systems for adipocyte lineage commitment. Conclusion: Understanding the role that adipogenic MSCs play during leukemia evolution and treatment could offer insight into pathogenesis and potential therapies for these disorders. Disclosures Liesveld: Onconova: Other: Data safety monitoring board; Astex: Honoraria; glycomimetics: Research Funding.

scholarly journals The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Angela Bentivegna ◽  
Gaia Roversi ◽  
Gabriele Riva ◽  
Laura Paoletta ◽  
Serena Redaelli ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Potential ◽  
Marrow Mesenchymal Stem Cells

Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic DNA in order to delineate a kind of methylation signature specific for early and late passages of culture. In the present work we focused on the modification of the methylation profiles of the X chromosome and imprinted loci, as sites expected to be more stable than whole genome. We propose a model where cultured hBM-MSCs undergo random modifications at the methylation level of most CGIs, nevertheless reflecting the original methylation status. We also pointed out global genome-wide demethylation connected to the long-term culture and senescence. Modification at CGIs promoters of specific genes could be related to the decrease in adipogenic differentiation potential. In conclusion, we showed important changes in CGIs methylation due to long-termin vitroculture that may affect the differentiation potential of hBM-MSCs. Therefore it is necessary to optimize the experimental conditions forin vitroexpansion in order to minimize these epigenetic changes and to standardize safer procedures.

scholarly journals Bone Marrow Mesenchymal Stem Cells Regulate IL-4 and INF-γ Expression in AR Mouse Model

2020 ◽  
Author(s):  
Chuanliang Zhao ◽  
Jingwen Sun ◽  
Xiaojing Cai ◽  
Wentao Zou ◽  
Jiaxiong Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Th1 Cell ◽  
Differentiation Potential ◽  
Th2 Cell ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Bone marrow mesenchymal stem cells can promote the recovery of immune balance and regulate the balance of Th1/2 cells. Allergic rhinitis is a disease with Th1/2 imbalance mediated by IgE. It’s unclear whether BMSCs could regulate AR disease. In this study, the possible role of BMSCs was explored. Methods : AR mouse model was established by ovalbumin (OVA). 18 models were randomly divided into three groups: AR-sensitized, Stem-cell-returned, Medium-returned; six unsensitized mouses named normal-control. IgE, IL-4 and INF-γ levels were measured by Elisa. Observing migration of BMSCs by immunofluorescence. Flow cytometry used to detect changes of Th1/2. STAT 4/6 protein level was detected by Western-blot. Results : After OVA-sensitization, IgE, IL-4 and STAT6 levels were higher, INF-γ and STAT4 level was lower. Flow cytometry revealed a decrease in Th1 cell and an increase in Th2 cell in AR group. After BMSCs treatment, t IgE, IL-4 and STAT6 levels in SCRg and MRg were lower than that in AR group, and tINF-γ and STAT4 level were higher than hat inAR group. Flow cytometry showed that the content of Th1 cell increased while Th2 cell decreased. Conclusions: BMSCs return treatment could decrease the expression of IL-4, promote the expression of INF-γ and regulate the balance of Th cell, and the mechanism was closely related to STAT4/6 signaling pathway. However there was no statistical difference between SCRg and MRg, so the role of BMSCs maybe achieved through paracrine function rather than multi-directional differentiation potential.

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