In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding

Fan, Chen; Lim, Lay Keng Priscilla; Wu, Zihao; Sharma, B.S.; Gan, Shi Qi; Liang, Kun; Upton, Zee; Leavesley, David I.

doi:10.3791/61037

Cited by 5 publications

(3 citation statements)

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“…In accordance with previous publications, several other organspecific fibrotic models induced by MMC supplementation have been developed (Chen et al, 2009;Graupp et al, 2015;Graupp et al, 2018;Fan et al, 2019;Good et al, 2019;Fan et al, 2020;Rønnow et al, 2020;De Pieri et al, 2021). It is worth noting that cocktails of pro-inflammatory cytokines have been used for more accurate recapitulation of fibrosis in vitro (Chawla and Ghosh, 2018) and such approach should be studied further in the future in combination with MMC.…”

Section: Discussionmentioning

confidence: 61%

“…In 2009, the first pathophysiologically relevant in vitro fibrosis model (termed Scar-in-the-Jar ) was published that utilised the principles of MMC (to enhance and accelerate ECM deposition) and TGF β 1 (to induce myofibroblast transformation of WI-38 lung fibroblasts) ( Chen et al, 2009 ). Since then, several fibrotic models based on MMC have been developed for screening anti-fibrotics in different fibrotic diseases (e.g., dermal ( Fan et al, 2019 ; Fan et al, 2020 ), lung ( Good et al, 2019 ; Rønnow et al, 2020 ), vocal fold ( Graupp et al, 2015 ; Graupp et al, 2018 ) scarring). Unfortunately, these dermal scar models might be incomplete as the optimal crowding molecule was not used ( Chen et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies

Coentro

May

Prince

et al. 2021

Front. Bioeng. Biotechnol.

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Skin fibrosis still constitutes an unmet clinical need. Although pharmacological strategies are at the forefront of scientific and technological research and innovation, their clinical translation is hindered by the poor predictive capacity of the currently available in vitro fibrosis models. Indeed, customarily utilised in vitro scarring models are conducted in a low extracellular matrix milieu, which constitutes an oxymoron for the in-hand pathophysiology. Herein, we coupled macromolecular crowding (enhances and accelerates extracellular matrix deposition) with transforming growth factor β1 (TGFβ1; induces trans-differentiation of fibroblasts to myofibroblasts) in human dermal fibroblast cultures to develop a skin fibrosis in vitro model and to screen a range of anti-fibrotic families (corticosteroids, inhibitors of histone deacetylases, inhibitors of collagen crosslinking, inhibitors of TGFβ1 and pleiotropic inhibitors of fibrotic activation). Data obtained demonstrated that macromolecular crowding combined with TGFβ1 significantly enhanced collagen deposition and myofibroblast transformation. Among the anti-fibrotic compounds assessed, trichostatin A (inhibitors of histone deacetylases); serelaxin and pirfenidone (pleiotropic inhibitors of fibrotic activation); and soluble TGFβ receptor trap (inhibitor of TGFβ signalling) resulted in the highest decrease of collagen type I deposition (even higher than triamcinolone acetonide, the gold standard in clinical practice). This study further advocates the potential of macromolecular crowding in the development of in vitro pathophysiology models.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies

Coentro

May

Prince

et al. 2021

Front. Bioeng. Biotechnol.

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“…Crowders such as ficolls and dextrans of differing molecular weights are meant to take up a fractional volume of the media to mimic fibrosis where ECM crowds cells in vivo. Such techniques, termed macromolecular crowding, should be incorporated into in vitro models in future work [127,128].…”

Section: Cellularmentioning

confidence: 99%

The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

Carney¹,

Shupp²,

Travis³

2022

Recent Advances in Wound Healing

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Hypertrophic scar (HTS) is a fibrotic skin disorder that is marked by excessive inflammation and extracellular matrix deposition in response to cutaneous traumatic injuries such as burns, lacerations, incisions, and abrasions. HTS has various risk factors, available treatments, and treatment effectiveness. Research at the basic, translational, and clinical levels are in their infancy compared to fibrotic diseases in other organ systems. This chapter will review current in vitro and in vivo modeling, and highlight research needs to address gaps in the study of HTS. The following topics will be discussed in the chapter: a. Basic Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research b. Translational Science Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research c. Clinical Research i. Seminal findings ii. Limitations to these models iii. Suggestions for topics of future research.

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Macromolecular crowding in the development of a three-dimensional organotypic human breast cancer model

et al. 2022

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In Vitro Model of Human Cutaneous Hypertrophic Scarring using Macromolecular Crowding

Cited by 5 publications

References 0 publications

Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies

Adapting the Scar-in-a-Jar to Skin Fibrosis and Screening Traditional and Contemporary Anti-Fibrotic Therapies

The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars

Macromolecular crowding in the development of a three-dimensional organotypic human breast cancer model

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