Engineering Advanced In Vitro Models of Systemic Sclerosis for Drug Discovery and Development
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Published on: May 11, 2021
Andrea De Pieri1, Benjamin D Korman2, Astrid Jüngel3,4
1Dr. A. De Pieri, Prof. K. Wuertz-Kozak, Department of Biomedical Engineering, Rochester Institute of Technology (RIT), 106 Lomb Memorial Rd., Rochester, NY, 14623, USA.
Abstract:
Systemic sclerosis (SSc) is a complex multisystem disease with the highest case-specific mortality among all autoimmune rheumatic diseases, yet without any available curative therapy. Therefore, the development of novel therapeutic antifibrotic strategies that effectively decrease skin and organ fibrosis is needed. Existing animal models are cost-intensive, laborious and do not recapitulate the full spectrum of the disease and thus commonly fail to predict human efficacy. Advanced in vitro models, which closely mimic critical aspects of the pathology, have emerged as valuable platforms to investigate novel pharmaceutical therapies for the treatment of SSc. This review focuses on recent advancements in the development of SSc in vitro models, sheds light onto biological (e.g., growth factors, cytokines, coculture systems), biochemical (e.g., hypoxia, reactive oxygen species) and biophysical (e.g., stiffness, topography, dimensionality) cues that have been utilized for the in vitro recapitulation of the SSc microenvironment, and highlights future perspectives for effective drug discovery and validation.
Insights
Systemic sclerosis (SSc) treatment needs new antifibrotic therapies. Advanced in vitro models offer promising platforms for developing and validating novel drugs for this complex autoimmune disease.
Area of Science:
- Rheumatology and Immunology
- Translational Medicine
- Biomedical Engineering
Background:
- Systemic sclerosis (SSc) is a severe autoimmune disease with high mortality and no cure.
- Current animal models for SSc research are limited in predicting human treatment efficacy.
- There is a critical need for effective antifibrotic therapies to combat SSc-related fibrosis.
Purpose of the Study:
- To review advancements in in vitro models for Systemic sclerosis research.
- To explore biological, biochemical, and biophysical cues used to mimic the SSc microenvironment.
- To highlight future perspectives for drug discovery and validation in SSc treatment.
Main Methods:
- Review of recent literature on in vitro models for Systemic sclerosis.
- Analysis of biological factors (growth factors, cytokines, cocultures) in SSc models.
- Examination of biochemical (hypoxia, ROS) and biophysical (stiffness, topography) cues.
Main Results:
- Advanced in vitro models are emerging as valuable tools for SSc research.
- These models incorporate various cues to better recapitulate the SSc microenvironment.
- Progress in in vitro modeling aids in investigating novel pharmaceutical therapies for SSc.
Conclusions:
- In vitro models are crucial for overcoming limitations of traditional animal models in SSc.
- Utilizing diverse cues enhances the predictive power of in vitro systems for SSc therapies.
- Future development of these models holds significant promise for SSc drug discovery and validation.
