A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta

McClellan, Alyce; Evans, R. T.; Sze, Cheryl; Kan, Shohei; Paterson, Yasmin Z; Guest, Deborah J.

doi:10.1038/s41598-019-39370-4

Cited by 28 publications

(73 citation statements)

References 73 publications

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“…3.2 × 10 4 to 5.6 × 10 4 live cells per construct compared with the 8 × 10 4 cells per construct that were seeded). This cell survival range is similar to that which we have reported previously for static cultures (Barsby et al, 2014; McClellan, Evans, et al, 2019).…”

Section: Resultssupporting

confidence: 91%

“…The tenocytes used in this paper had been characterised previously for their gene expression and ability to contract a collagen gel when used at a similar range of passages (Barsby et al, 2014; Barsby & Guest, 2013; Bavin et al, 2017; McClellan, Evans, et al, 2019). When cultured in the bioreactor, the tenocytes are able to contract a collagen gel in a similar manner to static conditions, with both cyclic and static cultures producing tendon‐like constructs that have reached their maximum contraction of less than 20% the original starting size by day 14 of culture (Figure 3a).…”

Section: Resultsmentioning

confidence: 99%

“…The resulting tendon‐like constructs were characterised using gene expression, histology and immunohistochemistry to demonstrate the organisation of the collagen fibres, expression of tendon genes and distribution of extracellular tendon proteins within the matrix (Barsby et al, 2014). The static 3D culture system has further been used to determine the role of the tendon progenitor marker scleraxis at different stages of tendon development (Bavin et al, 2017) and monitor the functional effect of IL‐1β on tendon cells (McClellan, Evans, et al, 2019). However, this model did not account for the significant mechanical forces which the tendon cells are exposed to in vivo and we have not previously assessed the chemical composition and structural integrity of the resulting tendon constructs.…”

Section: Discussionmentioning

confidence: 99%

“…Dynamic shear analysis (DSA) was performed as described previously (Chaudhury, Holland, Vollrath, & Carr, 2011; McClellan, Evans, et al, 2019) using an AR 2000 rheometer (TA Instruments, New Castle, USA). Entire tendon‐like constructs were used (after 14 days of culture) and loaded in a coiled shape in order to create an area under the geometry that was filled with material.…”

Section: Methodsmentioning

confidence: 99%

“…Reorganisation of the collagen matrix to generate tendon‐like constructs is an important property of tenocytes, and collagen gel contraction is commonly used as a measure of cell‐mediated matrix reorganisation (Bell, Ivarsson, & Merrill, 1979; Montesano & Orci, 1988; Ngo, Ramalingam, Phillips, & Furuta, 2006; Yang et al, 2015). We have previously utilised three‐dimensional (3D) culture in a collagen gel to drive tendon differentiation by equine pluripotent stem cells (Barsby, Bavin, & Guest, 2014; Bavin, Smith, Baird, Smith, & Guest, 2015) and to determine the implications of gene knock‐down (Bavin, Atkinson, Barsby, & Guest, 2017) and inflammation (McClellan, Evans, et al, 2019) on tendon cell function. However, our previous model did not account for the significant mechanical forces that tendon cells are exposed to in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Cyclical strain improves artificial equine tendon constructs in vitro

Atkinson

Evans

Guest³

et al. 2020

J Tissue Eng Regen Med

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Tendon injuries are a common cause of morbidity in humans. They also occur frequently in horses, and the horse provides a relevant, large animal model in which to test novel therapies. To develop novel cell therapies that can aid tendon regeneration and reduce subsequent reinjury rates, the mechanisms that control tendon tissue regeneration and matrix remodelling need to be better understood. Although a range of chemical cues have been explored (growth factors, media etc.), the influence of the mechanical environment on tendon cell culture has yet to be fully elucidated. To mimic the in vivo environment, in this study, we have utilised a novel and affordable, custom-made bioreactor to apply a cyclical strain to tendon-like constructs generated in three-dimensional (3D) culture by equine tenocytes. Dynamic shear analysis (DSA), dynamic scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy were used to determine the mechanical and chemical properties of the resulting tendon-like constructs. Our results demonstrate that equine tenocytes exposed to a 10% cyclical strain have an increased amount of collagen gel contraction after 7 and 8 days of culture compared with cells cultured in 3D in the absence of external strain.While all the tendon-like constructs have a very similar chemical composition to native tendon, the application of strain improves their mechanical properties. We envisage that these results will contribute towards the development of improved biomimetic artificial tendon models for the development of novel strategies for equine regenerative therapies. K E Y W O R D S3D culture, dynamic shear analysis, equine, mechanical properties, tendon cells

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cyclical strain improves artificial equine tendon constructs in vitro

Atkinson

Evans

Guest³

et al. 2020

J Tissue Eng Regen Med

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SARS‐CoV‐2‐mediated immune system activation and potential application in immunotherapy

Tan

Tang

2020

Medicinal Research Reviews

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Although novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐mediated pulmonary inflammation has recently attracted great attention, its pathology and pathogenesis are not clear. Notably, due to both its high infective and pathogenicity, SARS‐CoV‐2 infection may cause a severe sometimes fatal respiratory disease. A specific vaccine, which relies on the analysis of SARS‐CoV‐2 structural protein‐derived antigenic peptides, is indispensable for restraining the spread and reducing the mortality of SARS‐CoV‐2. SARS‐CoV‐2 infections activate cytototxic, myeloid‐derived suppressor cells, dendritic cells, macrophages, as well as natural killer, B, helper T, and regulatory T cells, thus further stimulating innate and antigen‐specific immune responses. Nevertheless, many immune effector cells cause hyperinflammation and pulmonary immunopathology by releasing proinflammatory cytokines and chemokines, including interferon (IFN)‐α, IFN‐β, IFN‐γ, monocyte chemoattractant protein‐1, macrophage inflammatory protein (MIP)‐1A, MIP1B, interleukin (IL)‐1, IL‐2, IL‐4, IL‐6, IL‐7, IL‐8, IL‐9, IL‐12, IL‐17, and IL‐18, platelet‐derived growth factor, fibroblast growth factor, tumor necrosis factor‐α, and induced protein 10. Interestingly, related products derived from SARS‐CoV‐2 are likely to trigger immune evasion. Therefore, investigating SARS‐CoV‐2‐specific vaccines, blocking immunopathology, and prohibiting immune evasion are urgently required for treating SARS‐CoV‐2 infection. In this review, we emphatically illuminated the development of a SARS‐CoV‐2‐specific vaccine based on the analysis of epitopes, also expounding the molecular mechanisms of SARS‐CoV‐2‐mediated cytokine release syndrome. Furthermore, we comprehensively discussed SARS‐CoV‐2‐associated immune evasion and lung immunopathology. Lastly, potential therapeutic strategies against SARS‐CoV‐2 were explored.

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