Preconditioning of bone marrow-derived mesenchymal stem cells with N-acetyl-L-cysteine enhances bone regeneration via reinforced resistance to oxidative stress

Watanabe, Jobu; Yamada, Masahiro; Niibe, Kunimichi; Zhang, Maolin; Kondo, Takeru; Ishibashi, Minoru; Egusa, Hiroshi

doi:10.1016/j.biomaterials.2018.08.055

Cited by 67 publications

(49 citation statements)

References 61 publications

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“…Excessive oxidative stress may inhibit osteogenic differentiation of BMSCs 52–54. We found that the porous Se@SiO 2 nanocomposite protected BMSCs against H 2 O 2 -induced inhibition of osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 77%

Porous Se@SiO2 nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model

Li¹,

Wang²,

Liu³

et al. 2019

IJN

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Background: Delay or failure of bone union is a significant clinical challenge all over the world, and it has been reported that bone marrow mesenchymal stem cells (BMSCs) offer a promising approach to accelerate bone fracture healing. Se can modulate the proliferation and differentiation of BMSCs. Se-treatment enhances the osteoblastic differentiation of BMSCs and inhibiting the differentiation and formation of mature osteoclasts. The purpose of this study was to assess the effects of porous Se@SiO 2 nanocomposite on bone regeneration and the underlying biological mechanisms. Methods: We oxidized Se 2- to develop Se quantum dots, then we used the Se quantum dots to form a solid Se@SiO 2 nanocomposite which was then coated with polyvinylpyrrolidone (PVP) and etched in hot water to synthesize porous Se@SiO 2 nanocomposite. We used XRD pattern to assess the phase structure of the solid Se@SiO 2 nanocomposite. The morphology of porous Se@SiO 2 nanocomposite were evaluated by scanning electron microscope (SEM) and the biocompatibility of porous Se@SiO 2 nanocomposite were investigated by cell counting kit-8 (CCK-8) assays. Then, a release assay was also performed. We used a Transwell assay to determine cell mobility in response to the porous Se@SiO 2 nanocomposite. For in vitro experiments, BMSCs were divided into four groups to detect reactive oxygen species (ROS) generation, cell apoptosis, alkaline phosphatase activity, calcium deposition, gene activation and protein expression. For in vivo experiments, femur fracture model of rats was constructed to assess the osteogenic effects of porous Se@SiO 2 nanocomposite. Results: In vitro, intervention with porous Se@SiO 2 nanocomposite can promote migration and osteogenic differentiation of BMSCs, and protect BMSCs against H 2 O 2 -induced inhibition of osteogenic differentiation. In vivo, we demonstrated that the porous Se@SiO 2 nanocomposite accelerated bone fracture healing using a rat femur fracture model. Conclusion: Porous Se@SiO 2 nanocomposite promotes migration and osteogenesis differentiation of rat BMSCs and accelerates bone fracture healing, and porous Se@SiO 2 nanocomposite may provide clinic benefit for bone tissue engineering.

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Section: Discussionmentioning

confidence: 77%

Porous Se@SiO2 nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model

Li¹,

Wang²,

Liu³

et al. 2019

IJN

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“…Incubating cells with nanoparticles causes an imbalance of antioxidants in a cellular oxidative state by increasing ROS and decreasing antioxidants. Reduced glutathione (GSH) is an important intracellular antioxidant that plays vital roles in protecting cells against oxidative stress [63]. The amount of GSH decreases in cells under oxidative stress due to its oxidation to glutathione disulfide (GSSG).…”

Section: Platinum Nps Impair Antioxidants In Thp-1 Cellsmentioning

confidence: 99%

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

Gurunathan

Jeyaraj

et al. 2020

IJMS

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The thermoplasmonic properties of platinum nanoparticles (PtNPs) render them desirable for use in diagnosis, detection, therapy, and surgery. However, their toxicological effects and impact at the molecular level remain obscure. Nanotoxicology is mainly focused on the interactions of nanostructures with biological systems, particularly with an emphasis on elucidating the relationship between the physical and chemical properties such as size and shape. Therefore, we hypothesized whether these unique anisotropic nanoparticles could induce cytotoxicity similar to that of spherical nanoparticles and the mechanism involved. Thus, we synthesized unique and distinct anisotropic PtNPs using lycopene as a biological template and investigated their biological activities in model human acute monocytic leukemia (THP-1) macrophages. Exposure to PtNPs for 24 h dose-dependently decreased cell viability and proliferation. Levels of the cytotoxic markers lactate dehydrogenase and intracellular protease significantly and dose-dependently increased with PtNP concentration. Furthermore, cells incubated with PtNPs dose-dependently produced oxidative stress markers including reactive oxygen species (ROS), malondialdehyde, nitric oxide, and carbonylated protein. An imbalance in pro-oxidants and antioxidants was confirmed by significant decreases in reduced glutathione, thioredoxin, superoxide dismutase, and catalase levels against oxidative stress. The cell death mechanism was confirmed by mitochondrial dysfunction and decreased ATP levels, mitochondrial copy numbers, and PGC-1α expression. To further substantiate the mechanism of cell death mediated by endoplasmic reticulum stress (ERS), we determined the expression of the inositol-requiring enzyme (IRE1), (PKR-like ER kinase) PERK, activating transcription factor 6 (ATF6), and activating transcription factor 4 ATF4, the apoptotic markers p53, Bax, and caspase 3, and the anti-apoptotic marker Bcl-2. PtNPs could activate ERS and apoptosis mediated by mitochondria. A proinflammatory response to PtNPs was confirmed by significant upregulation of interleukin-1-beta (IL-1β), interferon γ (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL-6). Transcriptomic and molecular pathway analyses of THP-1 cells incubated with the half maximal inhibitory concentration (IC50) of PtNPs revealed the altered expression of genes involved in protein misfolding, mitochondrial function, protein synthesis, inflammatory responses, and transcription regulation. We applied transcriptomic analyses to investigate anisotropic PtNP-induced toxicity for further mechanistic studies. Isotropic nanoparticles are specifically used to inhibit non-specific cellular uptake, leading to enhanced in vivo bio-distribution and increased targeting capabilities due to the higher radius of curvature. These characteristics of anisotropic nanoparticles could enable the technology as an attractive platform for nanomedicine in biomedical applications.

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“…Cell Apoptosis Detection. Apoptosis of cultured CD34+ progenitor cells was induced via exposure to a high level of H 2 O 2 [16]. After being cultured in Iscove's Modified Dulbecco's Medium containing 50 μmol/L or 100 μmol/L H 2 O 2 (323381, Sigma-Aldrich, St. Louis, USA) for 24 hours, CD34+ progenitor cells of the two groups (CD34+ cells on fibronectin and CD34+ cells on aortic scaffold) were washed with ice-cold PBS and digested in 0.25% trypsin solution.…”

Section: Cell Proliferationmentioning

confidence: 99%

Decellularized Aortic Scaffold Alleviates H₂O₂-Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis

Gao

Feng

Cui

et al. 2020

BioMed Research International

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Bone marrow-derived stem/progenitor cells have been utilized for cardiac or vascular repair after ischemic injury, but they are subject to apoptosis and immune rejection in the ischemic site. Multiple scaffolds were used as delivery tools to transplant stem/ progenitor cells; however, these scaffolds did not show intrinsically antiapoptotic or anti-inflammatory properties. Decellularized aortic scaffolds that facilitate cell delivery and tissue repair were prepared by removing cells of patient-derived aortic tissues. Scanning electron microscopy (SEM) showed cells attached well to the scaffold after culturing for 5 days. Live/dead staining showed most seeded cells survived at day 7 on a decellularized aortic scaffold. Ki67 staining demonstrated that decellularized aortic scaffold promoted proliferation of bone marrow-derived CD34+ progenitor cells. Apoptosis of CD34+ progenitor cells induced by H 2 O 2 at high concentration was significantly alleviated in the presence of decellularized aortic scaffolds, demonstrating a protective effect against oxidative stress-induced apoptosis. Furthermore, decellularized aortic scaffolds significantly reduced the expression of proinflammatory cytokines (IL-8, GM-CSF, MIP-1β, GRO-α, Entoxin, and GRO) concurrently with an increase in anti-inflammatory cytokines (IL-2 and TGF-β) released from CD34+ progenitor cells when exposed to H 2 O 2 at low concentration. Finally, neovascularization was observed by H&E and immunohistochemical staining 14 days after the decellularized aortic scaffolds were subcutaneously implanted in nude mice. is preclinical study demonstrates that the use of a decellularized aortic scaffold possessing antiapoptotic and anti-inflammatory properties may represent a promising strategy for cardiovascular repair after ischemic injury.

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Preconditioning of bone marrow-derived mesenchymal stem cells with N-acetyl-L-cysteine enhances bone regeneration via reinforced resistance to oxidative stress

Cited by 67 publications

References 61 publications

<p>Porous Se@SiO<sub>2</sub> nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model</p>

<p>Porous Se@SiO<sub>2</sub> nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model</p>

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

Decellularized Aortic Scaffold Alleviates H₂O₂-Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis

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Preconditioning of bone marrow-derived mesenchymal stem cells with N-acetyl-L-cysteine enhances bone regeneration via reinforced resistance to oxidative stress

Cited by 67 publications

References 61 publications

<p>Porous Se@SiO<sub>2</sub> nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model</p>

<p>Porous Se@SiO<sub>2</sub> nanocomposite promotes migration and osteogenic differentiation of rat bone marrow mesenchymal stem cell to accelerate bone fracture healing in a rat model</p>

Anisotropic Platinum Nanoparticle-Induced Cytotoxicity, Apoptosis, Inflammatory Response, and Transcriptomic and Molecular Pathways in Human Acute Monocytic Leukemia Cells

Decellularized Aortic Scaffold Alleviates H2O2-Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis

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Product

Resources

About

Decellularized Aortic Scaffold Alleviates H₂O₂-Induced Inflammation and Apoptosis in CD34+ Progenitor Cells While Driving Neovasculogenesis