Comparative study between human mesenchymal stem cells and etanercept as immunomodulatory agents in rat model of rheumatoid arthritis

Immunol Res. 2020 Oct;68(5):255-268. doi: 10.1007/s12026-020-09132-w.

Abstract

To compare human adipose tissue mesenchymal stem cells (AT-MSCs) and etanercept as immunomodulatory agents for collagen-induced arthritis (CIA). CIA was induced by rats' immunization with collagen type II (CII) in complete Freund's adjuvant in days 0 and 7. Before the onset of CIA, prevention group received five doses of AT-MSCS intraperitoneally. After establishment of arthritis, rats received either five doses of AT-MSCs or phosphate-buffered saline (PBS) intraperitoneally or six doses of etanercept subcutaneously. Clinical and histopathological evaluation were performed in all groups; serum levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and anti-collagen II were assessed by enzyme-linked immunosorbent assay (ELISA). A total percent of autoreactive T and regulatory T (Treg) cells were quantified using spleen immune histochemical analysis. AT-MSCs were able to delay the onset of CIA, suppress the ongoing clinical and histopathological signs, decrease serum levels of TNF-α and anti-collagen type II, and downregulate the autoreactive T cells as etanercept. AT-MSCs were more potent in Treg cells upregulation, producing high serum levels of IL10. AT-MSCs might have a therapeutic effect in CIA via their potency in immune cell education, representing an effective new promising approach in rheumatoid arthritis in human.

Keywords: CIA; Etanercept; Mesenchymal stem cells; Regulatory T cells; Rheumatoid arthritis.

Publication types

  • Comparative Study

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Collagen Type II / administration & dosage
  • Collagen Type II / immunology
  • Etanercept / therapeutic use*
  • Female
  • Freund's Adjuvant / administration & dosage
  • Freund's Adjuvant / immunology
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Mesenchymal Stem Cell Transplantation*
  • Rats
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antirheumatic Agents
  • Collagen Type II
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Freund's Adjuvant
  • Etanercept