Effects of Plasma Treatment on the Bioactivity of Alkali-Treated Ceria-Stabilised Zirconia/Alumina Nanocomposite (NANOZR)

Zirconia ceramics such as ceria-stabilized zirconia/alumina nanocomposites (nano-ZR) are applied as implant materials due to their excellent mechanical properties. However, surface treatment is required to obtain sufficient biocompatibility. In the present study, we explored the material surface functionalization and assessed the initial adhesion of rat bone marrow mesenchymal stem cells, their osteogenic differentiation, and production of hard tissue, on plasma-treated alkali-modified nano-ZR. Superhydrophilicity was observed on the plasma-treated surface of alkali-treated nano-ZR along with hydroxide formation and reduced surface carbon. A decreased contact angle was also observed as nano-ZR attained an appropriate wettability index. Treated samples showed higher in vitro bovine serum albumin (BSA) adsorption, initial adhesion of bone marrow and endothelial vascular cells, high alkaline phosphatase activity, and increased expression of bone differentiation-related factors. Furthermore, the in vivo performance of treated nano-ZR was evaluated by implantation in the femur of male Sprague–Dawley rats. The results showed that the amount of bone formed after the plasma treatment of alkali-modified nano-ZR was higher than that of untreated nano-ZR. Thus, induction of superhydrophilicity in nano-ZR via atmospheric pressure plasma treatment affects bone marrow and vascular cell adhesion and promotes bone formation without altering other surface properties.

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Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium tuberculosis at Its Bone Marrow Niche

Pathogens ◽

10.3390/pathogens9050372 ◽

2020 ◽

Vol 9 (5) ◽

pp. 372 ◽

Cited By ~ 1

Author(s):

Jaishree Garhyan ◽

Surender Mohan ◽

Vinoth Rajendran ◽

Rakesh Bhatnagar

Keyword(s):

Bone Marrow ◽

Mycobacterium Tuberculosis ◽

In Vitro Release ◽

Bone Marrow Niche ◽

Mice Model ◽

Latently Infected ◽

Marrow Mesenchymal Stem Cells

One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 ± 16.3 nm and 84 ± 18.4 nm, respectively, with the encapsulation efficiency of 69.5% ± 4.2% and 70.6% ± 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells.

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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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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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Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia

AJP Cell Physiology ◽

10.1152/ajpcell.00392.2018 ◽

2019 ◽

Vol 316 (6) ◽

pp. C815-C827 ◽

Cited By ~ 5

Author(s):

Yinyan Yue ◽

Ziqiang Luo ◽

Zhengchang Liao ◽

Liming Zhang ◽

Shuai Liu ◽

...

Keyword(s):

Bone Marrow ◽

Lung Development ◽

Bone Marrow Mscs ◽

Mk 801 ◽

Intrauterine Hypoxia ◽

Marrow Mesenchymal Stem Cells ◽

Cell Cycling ◽

Excessive Activation

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

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