Defective Antiviral Responses of Induced Pluripotent Stem Cells to Baculoviral Vector Transduction

Chen, Guan-Yu; Hwang, Shiaw-Min; Su, H.; Kuo, Chien-Yi; Luo, Wei; Lo, Kai-Wei; Huang, Cheng-Chieh; Chen, Chiu-Ling; Yu, Sheng-Han; Hu, Yu‐Chen

doi:10.1128/jvi.00808-12

Cited by 26 publications

(33 citation statements)

References 52 publications

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“…Therefore, the IFN system, which is the central part of innate immunity in differentiated somatic cells [14], is not fully functional in ESCs. Together with the similar findings in induced pluripotent stem cells [15] and embryonal carcinoma [16], an underdeveloped antiviral innate immunity represents an intrinsic property of all pluripotent cells (reviewed in Guo et al [17]). …”

Section: Introductionmentioning

confidence: 97%

Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells

D’Angelo

Acharya

Wang

et al. 2016

Stem Cells and Development

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The innate immunity of embryonic stem cells (ESCs) has recently emerged as an important issue in ESC biology and in ESC-based regenerative medicine. We have recently reported that mouse ESCs (mESCs) do not have a functional type I interferon (IFN)-based antiviral innate immunity. They are deficient in expressing IFN in response to viral infection and have limited ability to respond to IFN. Using fibroblasts (FBs) as a cell model, the current study investigated the development of antiviral mechanisms during in vitro differentiation of mESCs. We demonstrate that mESC-differentiated FBs (mESC-FBs) share extensive similarities with naturally differentiated FBs in morphology, marker expression, and growth pattern, but their development of antiviral mechanisms lags behind. Nonetheless, the antiviral mechanisms are inducible during mESC differentiation as demonstrated by the transition of nuclear factor kappa B (NFkB), a key transcription factor for IFN expression, from its inactive state in mESCs to its active state in mESC-FBs and by increased responses of mESC-FBs to viral stimuli and IFN during their continued in vitro propagation. Together with our previously published study, the current data provide important insights into molecular basis for the deficiency of IFN expression in mESCs and the development of antiviral innate immunity during mESC differentiation.

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Section: Introductionmentioning

confidence: 97%

Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells

D’Angelo

Acharya

Wang

et al. 2016

Stem Cells and Development

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“…Indeed, it has been demonstrated that ESCs do not show immune responses typically seen in differentiated cells when infected with bacteria and viruses (14,15). Our recent studies in mouse ESCs (mESCs) (16–18) and those from other investigators in human ESCs (hESCs) and in induced pluripotent stem cells (iPSCs) (19,20) demonstrated that the IFN system, the central component of innate antiviral immunity in differentiated somatic cells (21), is not fully developed in these cells. Therefore, the lack of innate immune responses to both bacterial and viral infection appears to be an intrinsic property of all pluripotent stem cells (10).…”

Section: Introductionmentioning

confidence: 99%

The Molecular Basis for the Lack of Inflammatory Responses in Mouse Embryonic Stem Cells and Their Differentiated Cells

D’Angelo

Gurung

Acharya

et al. 2017

The Journal of Immunology

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We have previously reported that mouse embryonic stem cells (mESCs) do not have a functional IFN-based antiviral mechanism. The current study extends our investigation to the inflammatory response in mESCs and mESC-differentiated cells. We demonstrate that LPS, TNFα, and viral infection, all of which induce robust inflammatory responses in naturally differentiated cells, failed to activate NFκB, the key transcription factor that mediates inflammatory responses, and were unable to induce the expression of inflammatory genes in mESCs. Similar results were obtained in human ESCs (hESCs). In addition to the inactive state of NFκB, the deficiency of inflammatory response in mESCs is also attributed to the lack of functional receptors for LPS and TNFα. In vitro differentiation can trigger the development of the inflammatory response mechanism, as indicated by the transition of NFκB from its inactive to active state. However, a limited response was observed in mESC-differentiated fibroblasts only to TNFα and viral infection, but not to LPS. We conclude that the inflammatory response mechanism is not active in mESCs, and in vitro differentiation promotes only partial development of this mechanism. Together with our previous studies, the findings described in this paper demonstrate that ESCs are fundamentally different from differentiated somatic cells in their innate immunity, which may have important implications in developmental biology, immunology and ESC-based regenerative medicine.

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“…Nayak et al 19 reported that graphene-treated human mesenchymal stem cells show enhanced proliferation and differentiation. Chen et al 20 reported that graphene and GO can support induced pluripotent stem cell culture and allow for spontaneous differentiation, and also suggested that the different surface properties of graphene and GO influence the performance of induced pluripotent stem cell culture and applications. The different physical and chemical properties could influence the biological responses of cells.…”

Section: Introductionmentioning

confidence: 99%

Ginkgo biloba: a natural reducing agent for the synthesis of cytocompatible graphene

Gurunathan¹,

Jw²,

Jh³

et al. 2014

IJN

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Background Graphene is a novel two-dimensional planar nanocomposite material consisting of rings of carbon atoms with a hexagonal lattice structure. Graphene exhibits unique physical, chemical, mechanical, electrical, elasticity, and cytocompatible properties that lead to many potential biomedical applications. Nevertheless, the water-insoluble property of graphene restricts its application in various aspects of biomedical fields. Therefore, the objective of this work was to find a novel biological approach for an efficient method to synthesize water-soluble and cytocompatible graphene using Ginkgo biloba extract (GbE) as a reducing and stabilizing agent. In addition, we investigated the biocompatibility effects of graphene in MDA-MB-231 human breast cancer cells. Materials and methods Synthesized graphene oxide (GO) and GbE-reduced GO (Gb-rGO) were characterized using various sequences of techniques: ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. Biocompatibility of GO and Gb-rGO was assessed in human breast cancer cells using a series of assays, including cell viability, apoptosis, and alkaline phosphatase (ALP) activity. Results The successful synthesis of graphene was confirmed by UV-vis spectroscopy and FTIR. DLS analysis was performed to determine the average size of GO and Gb-rGO. X-ray diffraction studies confirmed the crystalline nature of graphene. SEM was used to investigate the surface morphologies of GO and Gb-rGO. AFM was employed to investigate the morphologies of prepared graphene and the height profile of GO and Gb-rGO. The formation of defects in Gb-rGO was confirmed by Raman spectroscopy. The biocompatibility of the prepared GO and Gb-rGO was investigated using a water-soluble tetrazolium 8 assay on human breast cancer cells. GO exhibited a dose-dependent toxicity, whereas Gb-rGO-treated cells showed significant biocompatibility and increased ALP activity compared to GO. Conclusion In this work, a nontoxic natural reducing agent of GbE was used to prepare soluble graphene. The as-prepared Gb-rGO showed significant biocompatibility with human cancer cells. This simple, cost-effective, and green procedure offers an alternative route for large-scale production of rGO, and could be used for various biomedical applications, such as tissue engineering, drug delivery, biosensing, and molecular imaging.

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Defective Antiviral Responses of Induced Pluripotent Stem Cells to Baculoviral Vector Transduction

Cited by 26 publications

References 52 publications

Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells

Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells

The Molecular Basis for the Lack of Inflammatory Responses in Mouse Embryonic Stem Cells and Their Differentiated Cells

Ginkgo biloba: a natural reducing agent for the synthesis of cytocompatible graphene

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