3D Cell Culture as Tools to Characterize Rheumatoid Arthritis Signaling and Development of New Treatments

Abstract

Rheumatoid arthritis (RA) is one of the most common autoimmune disorders affecting 0.5–1% of the population worldwide. As a disease of multifactorial etiology, its constant study has made it possible to unravel the pathophysiological processes that cause the illness. However, efficient and validated disease models are necessary to continue the search for new disease-modulating drugs. Technologies, such as 3D cell culture and organ-on-a-chip, have contributed to accelerating the prospecting of new therapeutic molecules and even helping to elucidate hitherto unknown aspects of the pathogenesis of multiple diseases. These technologies, where medicine and biotechnology converge, can be applied to understand RA. This review discusses the critical elements of RA pathophysiology and current treatment strategies. Next, we discuss 3D cell culture and apply these methodologies for rheumatological diseases and selected models for RA. Finally, we summarize the application of 3D cell culture for RA treatment.

2D and 3D culture of stem cells

“…Badania dowodzą że ich użycie zmniejsza stan zapalny i powoduje szybszą regenerację chrząstki. [24] Pod uwagę brane są również komórki układu nerwowego. Hoduje się komórki mikrogleju w tym astrocyty na hydrożelach kolagenowych, co pozwala na określenie działania leków używanych w chorobach otępiennych.…”

How to improve translatability and clinical relevance of preclinical studies in rheumatoid arthritis

“…The conventional in vitro systems used to study RA FLSs, albeit standardised, easy to set up and highly reproducible, are too simplistic and display critical weaknesses that compromise the clinical relevance of the results [20]. For example, even when primary FLSs from patients with RA were used, the cells were removed via enzymatic digestion from the pannus and the inflamed milieu of RA and then were passaged and cultured multiple times in monolayer two-dimensional (2D) cell culture systems [5].…”

“…For example, even when primary FLSs from patients with RA were used, the cells were removed via enzymatic digestion from the pannus and the inflamed milieu of RA and then were passaged and cultured multiple times in monolayer two-dimensional (2D) cell culture systems [5]. Under these experimental conditions, FLSs may change their phenotype through passaging/culturing, lose the continuous exposure to arthritogenic mediators and lack their interaction with extracellular matrix (ECM) and other cell types (e.g., synovial macrophages, osteoclasts, chondrocytes, T-and B-lymphocytes) [20].…”

“…Recent development of three-dimensional (3D) cell culture technologies have revolutionised the modelling of human synovium at the different stages of RA [28]. These synovial organoids include scaffold-free culture, scaffoldbased culture (cells are seeded on hydrogel that simulates ECM) and microfluidics (joint-on-a-chip that allows chemical concentration gradients and control of shear stress and pressure on cells) [20,28]. The main advantage of these platforms over the conventional 2D in vitro systems is that they mimic FLSs interactions with ECM and other cell types [20].…”

“…These synovial organoids include scaffold-free culture, scaffoldbased culture (cells are seeded on hydrogel that simulates ECM) and microfluidics (joint-on-a-chip that allows chemical concentration gradients and control of shear stress and pressure on cells) [20,28]. The main advantage of these platforms over the conventional 2D in vitro systems is that they mimic FLSs interactions with ECM and other cell types [20]. RA exhibits molecular, cellular, genetic, clinical and therapeutic heterogeneity [27].…”