Bone Marrow Mesenchymal Stem Cells Derived Discoidin Domain-Containing Receptor 2 (DDR2) as a Communication Mediator to Strengthen the Invasiveness and Metastasis of Papillary Thyroid Carcinoma

Our current study plans to dissect the impacts and its underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on the invasive and metastatic features of PTC. Clinical specimens from distantly metastatic PTC were collected to measure DRR2 level. After being identified via tri-lineage differentiation and flow cytometry, BMSCs were co-cultured with PTC cells followed by analysis of cell proliferation and migration by CCK-8 and Transwell assays, expression of DDR2 and EMT-associated proteins by Western blot. Eventually, shDDR2-transfected BMSCs were infused with PTC cells into the abdominal cavity of mice to establish a mouse model assess their effect on tumor growth and distant metastasis. DDR2 was upregulated in BMSCs and malignant cells located in the metastatic sites. Co-culture with BMSCs enhanced DRR2 expression in PTC cells, which was simultaneously accompanied by the escalated mesenchymalization process. In vivo experiments exhibited that co-injection with BMSCs facilitated disease progression and distant metastasis of malignancies. Instead, DDR2 knockdown significantly impeded BMSCs-triggered migrative and proliferative behaviors of malignant cells. In conclusion, DDR2 derived from BMSCs can function as a communication mediator to strengthen the invasiveness and metastasis of PTC.

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Recombinant human BMP-2 accelerates the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway in vitro and in vivo

Biomaterials Science ◽

10.1039/c8bm00846a ◽

2019 ◽

Vol 7 (1) ◽

pp. 362-372 ◽

Cited By ~ 6

Author(s):

Shuhao Liu ◽

Yang Liu ◽

Libo Jiang ◽

Zheng Li ◽

Soomin Lee ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Marrow Mesenchymal Stem Cells

BMP-2-induced migration of BMSCs can be inhibited by silencing CDC42 in vitro and in vivo.

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Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

10.21203/rs.3.rs-850531/v1 ◽

2021 ◽

Author(s):

meng li ◽

ning yang ◽

li hao ◽

wei zhou ◽

lei li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

High Dose ◽

Treatment Pathways ◽

Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

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Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo

Cancer Letters ◽

10.1016/j.canlet.2011.10.002 ◽

2012 ◽

Vol 315 (1) ◽

pp. 28-37 ◽

Cited By ~ 238

Author(s):

Wei Zhu ◽

Ling Huang ◽

Yahong Li ◽

Xu Zhang ◽

Jianmei Gu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Tumor Growth ◽

Human Bone ◽

Human Bone Marrow ◽

Promote Tumor Growth ◽

Marrow Mesenchymal Stem Cells

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Human bone marrow mesenchymal stem cells in vivo

Rheumatology ◽

10.1093/rheumatology/kem206 ◽

2007 ◽

Vol 47 (2) ◽

pp. 126-131 ◽

Cited By ~ 172

Author(s):

E. Jones ◽

D. McGonagle

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Marrow Mesenchymal Stem Cells

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Abstract 2838: Bone Marrow Mesenchymal Stem Cells Differentiated into Beating Cardiomyocytes In Vivo and Improved Myocardial Function

Circulation ◽

10.1161/circ.116.suppl_16.ii_631-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Tong Wang ◽

Wanchun Tang ◽

Shijie Sun ◽

Min-shan Tsai ◽

Max Harry Weil

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Myocardial Function ◽

Phosphate Buffer Solution ◽

Sprague Dawley ◽

Buffer Solution ◽

Marrow Mesenchymal Stem Cells ◽

And Control

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)

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The negatively charged microenvironment of collagen hydrogels regulates the chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

Journal of Materials Chemistry B ◽

10.1039/d0tb00172d ◽

2020 ◽

Vol 8 (21) ◽

pp. 4680-4693

Author(s):

Jirong Yang ◽

Yumei Xiao ◽

Zizhao Tang ◽

Zhaocong Luo ◽

Dongxiao Li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Protein Adsorption ◽

Cell Morphology ◽

Chondrogenic Differentiation ◽

Collagen Hydrogels ◽

Marrow Mesenchymal Stem Cells

The different negatively charged microenvironments of collagen hydrogels affect the protein adsorption, cell morphology, and chondrogenic differentiation of BMSCs in vitro and in vivo.

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Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair

Nanomedicine ◽

10.2217/nnm-2019-0208 ◽

2020 ◽

Vol 15 (3) ◽

pp. 273-288 ◽

Cited By ~ 1

Author(s):

Chun Liu ◽

Yun Li ◽

Zhijian Yang ◽

Zhiyou Zhou ◽

Zhihao Lou ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Therapeutic Effect ◽

Bone Marrow Mscs ◽

In Vivo Experiments ◽

Marrow Mesenchymal Stem Cells ◽

Cartilage Diseases

The effectiveness of mesenchymal stem cells (MSC) in the treatment of cartilage diseases has been demonstrated to be attributed to the paracrine mechanisms, especially the mediation of exosomes. But the exosomes derived from unsynchronized MSCs may be nonhomogeneous and the therapeutic effect varies between samples. Aim: To produce homogeneous and more effective exosomes for the regeneration of cartilage. Materials & methods: In this study we produced specific exosomes from bone marrow MSCs (BMSC) through kartogenin (KGN) preconditioning and investigated their performance in either in vitro or in vivo experiments. Results & conclusion: The exosomes derived from KGN-preconditioned BMSCs (KGN-BMSC-Exos) performed more effectively than the exosomes derived from BMSCs (BMSC-Exos). KGN preconditioning endowed BMSC-Exos with stronger chondral matrix formation and less degradation.

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Acceleration of Bone Regeneration in Critical-Size Defect Using BMP-9-Loaded nHA/ColI/MWCNTs Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells

BioMed Research International ◽

10.1155/2019/7343957 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Ran Zhang ◽

Xuewen Li ◽

Yao Liu ◽

Xiaobo Gao ◽

Tong Zhu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Composite Scaffold ◽

Marrow Mesenchymal Stem Cells

Biocompatible scaffolding materials play an important role in bone tissue engineering. This study sought to develop and characterize a nano-hydroxyapatite (nHA)/collagen I (ColI)/multi-walled carbon nanotube (MWCNT) composite scaffold loaded with recombinant bone morphogenetic protein-9 (BMP-9) for bone tissue engineering by in vitro and in vivo experiments. The composite nHA/ColI/MWCNT scaffolds were fabricated at various concentrations of MWCNTs (0.5, 1, and 1.5% wt) by blending and freeze drying. The porosity, swelling rate, water absorption rate, mechanical properties, and biocompatibility of scaffolds were measured. After loading with BMP-9, bone marrow mesenchymal stem cells (BMMSCs) were seeded to evaluate their characteristics in vitro and in a critical sized defect in Sprague-Dawley rats in vivo. It was shown that the 1% MWCNT group was the most suitable for bone tissue engineering. Our results demonstrated that scaffolds loaded with BMP-9 promoted differentiation of BMMSCs into osteoblasts in vitro and induced more bone formation in vivo. To conclude, nHA/ColI/MWCNT scaffolds loaded with BMP-9 possess high biocompatibility and osteogenesis and are a good candidate for use in bone tissue engineering.

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