Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development

Pieri, Andrea De; Korman, Benjamin; Jüngel, Astrid; Wuertz‐Kozak, Karin

doi:10.1002/adbi.202000168

Cited by 11 publications

(11 citation statements)

References 326 publications

(303 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with previous publications, several other organ-specific 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: 59%

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.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 59%

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.

View full text Add to dashboard Cite

show abstract

“…When addressing the role of the epidermis and dermis in SSc pathogenesis, it has to be taken into consideration that these anatomical structures are not faithfully reproduced in in vitro systems in which both keratinocytes and fibroblasts are cultured in 2D systems and when the respective conditioned media are used to stimulate the cell counterpart. Although a method for isolating and culturing skin cells, including endothelial cells, fibroblasts, keratinocytes, and melanocytes from small SSc skin biopsies has been published [ 7 ], increased efforts in the field of tissue engineering have recently led to the development of 3D human models with improved intercellular interactions and tissue microenvironment observed in skin fibrosis [ 8 ]. Self-assembled or scaffold-based models exploit the ability of fibroblasts to generate 3D dermal-like constructs, producing their own ECM.…”

Section: Progress In Reconstituted Skin Modelsmentioning

confidence: 99%

Contribution of keratinocytes to dermal fibrosis

Russo

Brembilla

Chizzolini

2022

Current Opinion in Rheumatology

View full text Add to dashboard Cite

Purpose of reviewThe cellular pathogenesis of fibrotic disorders including systemic sclerosis (SSc) remains largely speculative. Currently, the altered function of endothelial cells and fibroblasts under the influence of an inappropriate immune response are considered central pathogenic events in SSc. Adding to this complexity, novel evidence here reviewed suggests that keratinocytes may concur in the development of skin fibrosis.Recent findingsEpidermal equivalents (EE) generated from primary SSc keratinocytes display a distinct gene expression program when compared to healthy donor (HD) EE. SSc-EE, among others, exhibited enhanced oxidative and metabolic response pathways. Immunohistochemical studies demonstrated similarities between SSc-EE and SSc epidermis including altered keratinocyte differentiation, enhanced expression of activation markers, and reduced rate of basal keratinocytes proliferation. SSc-EE supernatants more than HD-EE modified the inflammatory and extracellular matrix deposition/resorption program of dermal fibroblasts. Further evidence indicated that the relative lack rather than the excess of interleukin-25 in keratinocytes may contribute to enhanced dermal fibrotic changes. Overall, these data support keratinocyte-intrinsic SSc-related modifications.SummaryImproved methods for engineering epidermal and skin equivalents are helping to address the question whether keratinocyte alterations in SSc are primary and capable to dysregulate dermal homeostasis or secondary following dermal fibrotic changes.

show abstract

“…An in vitro model is a logical first experiment to test the response of the OC scaffold as it is the cheapest, lowest risk and fastest way to generate biological results (Table 3) [230][231][232]. Greater cell density, proliferation, and migration in the subchondral bone phase over the cartilage.…”

Section: Functional Evaluation: In Vitro and In Vivomentioning

confidence: 99%

3D Printed Multiphasic Scaffolds for Osteochondral Repair: Challenges and Opportunities

Doyle

Snow

Duchi

et al. 2021

IJMS

View full text Add to dashboard Cite

Osteochondral (OC) defects are debilitating joint injuries characterized by the loss of full thickness articular cartilage along with the underlying calcified cartilage through to the subchondral bone. While current surgical treatments can provide some relief from pain, none can fully repair all the components of the OC unit and restore its native function. Engineering OC tissue is challenging due to the presence of the three distinct tissue regions. Recent advances in additive manufacturing provide unprecedented control over the internal microstructure of bioscaffolds, the patterning of growth factors and the encapsulation of potentially regenerative cells. These developments are ushering in a new paradigm of ‘multiphasic’ scaffold designs in which the optimal micro-environment for each tissue region is individually crafted. Although the adoption of these techniques provides new opportunities in OC research, it also introduces challenges, such as creating tissue interfaces, integrating multiple fabrication techniques and co-culturing different cells within the same construct. This review captures the considerations and capabilities in developing 3D printed OC scaffolds, including materials, fabrication techniques, mechanical function, biological components and design.

show abstract

Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development

Cited by 11 publications

References 326 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

Contribution of keratinocytes to dermal fibrosis

3D Printed Multiphasic Scaffolds for Osteochondral Repair: Challenges and Opportunities

Contact Info

Product

Resources

About