A Three-Dimensional Co-Culture Model for Rheumatoid Arthritis Pannus Tissue.

Jietao Lin,Jian Li,Liqing Ke,Jianhai Chen,Antonia Rujia Sun,Shengli Mi,Peng Zhang,Tianying Yuan,Wenxiang Cheng,Wei Sun

doi:10.3389/fbioe.2021.764212

Abstract

Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.

Highlights

Joint is a dynamic tissue that supports us to move, but it may suffer destruction of bone and cartilage because of arthritis like rheumatoid arthritis (RA)
We report the construction of in vitro RA pannus co-culture model by applying 3D printing technique with EA.hy 926/MH7A and gelatin/alginate
The 3D pannus model showed a good cell viability and interaction to mimic the microenvironment of pannus in vivo

Summary

Introduction

Joint is a dynamic tissue that supports us to move, but it may suffer destruction of bone and cartilage because of arthritis like RA. New vessels and hyperplastic fibrous tissue contribute to angiogenic disorders and form a complex vascular tissue called pannus (Veale et al, 2017). RA pannus is an aggressive and invasive tissue with massive leukocyte infiltration, proliferative synovial membranes and neovascularization, which is directly responsible for cartilage destruction and bone erosion (Lee and Weinblatt, 2001). The development of pannus is highly relevant to the growth factors, pro-inflammatory cytokines and chemokines. Growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are described as the key regulators

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