Latest models for the discovery and development of rheumatoid arthritis drugs

ABSTRACT

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease that reduces the quality of life. The current speed of development of therapeutic agents against RA is not satisfactory. Models on which initial experiments are conducted do not fully reflect human pathogenesis. Overcoming this oversimplification might be a crucial step to accelerate studies on RA treatment.

Areas covered

The current approaches to produce novel models or to improve currently available models for the development of RA drugs have been discussed. Advantages and drawbacks of two- and three-dimensional cell cultures and animal models have been described based on recently published results of the studies. Moreover, approaches such as tissue engineering or organ-on-a-chip have been reviewed.

Expert opinion

The cell cultures and animal models used to date appear to be of limited value due to the complexity of the processes involved in RA. Current models in RA research should take into account the heterogeneity of patients in terms of disease subtypes, course, and activity. Several advanced models and tools using human cells and tissues have been developed, including three-dimensional tissues, liquid bioreactors, and more complex joint-on-a-chip devices. This may increase knowledge of the molecular mechanisms leading to disease development, to help identify new biomarkers for early detection, and to develop preventive strategies and more effective treatments.

KEYWORDS:

• Rheumatoid arthritis
• models
• animal models
• organ-on-a-chip

Article highlights

• Despite the development of novel technologies, two-dimensional cell cultures and animal models are easily feasible, widely used, and, therefore, provide a vast amount of data on rheumatoid arthritis (RA) pathogenesis and therapies.

• Induced pluripotent stem cells are a new treatment, promoting a regenerative function in mature cells prepared in vivo.

• Three-dimensional technology and tissue explants are useful tools that replicate accurately bone structure, joint microenvironment, or mechanistic processes, all of which are helpful in investigating RA pathogenesis.

• Constructing such devices as liver, kidney, or synovium on a chip has enabled further exploration of the interactions between cells, which may lead to a better understanding of RA management or drug development.

• Mathematical models are used to simulate illness without performing clinical trials on patients.

Acknowledgments

The authors would like to thank Piotr Michalski from the Academy of Art in Szczecin for his assistance in composing the figures.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.