Human umbilical cord mesenchymal stem cells improve the immune-associated inflammatory and prothrombotic state in collagen type-Ⅱ-induced arthritic rats

Mol Med Rep. 2015 Nov;12(5):7463-70. doi: 10.3892/mmr.2015.4394. Epub 2015 Sep 30.

Abstract

Human umbilical cord mesenchymal stem cells (hUC‑MSCs) hold great potential in the search for therapies to treat refractory diseases, including rheumatoid arthritis (RA), due to their potential regenerative ability and extensive source. However, the role of hUC‑MSCs in vivo and the repair mechanisms for RA remain to be fully elucidated. The present study aimed to determine whether hUC‑MSCs exert immunomodulatory effects and have anti‑inflammatory capabilities in the treatment of embolisms. Following the transplantation of hUC‑MSCs into collagen type Ⅱ‑induced arthritic (CIA) model rats, magnetic resonance imaging (MRI) in vivo was performed, and the levels of interleukin (IL)‑1, IL‑17, tumor necrosis factor (TNF)‑α, vascular endothelial growth factor (VEGF), tissue factor (TF), CD4+CD25+ T cells (Treg) and antithrombin (AT) were measured. Bromodeoxyuridine staining was performed for histopathological examinations. As revealed by immunofluorescence and MRI experiments, the injected hUC‑MSCs preferentially migrated to the inflammatory joint sites of the rats. The Treg cell percentage and AT levels in the hUC‑MSC‑treated group were markedly increased, whereas the levels of IL‑1, IL‑17, TNF‑α, VEGF and TF were decreased compared with those in the CIA model group. The values determined for these parameters in the hUC‑MSC‑treated group returned to approximately the identical values as those of the control group on day 35 post‑therapy. Superparamagnetic iron oxide nanoparticles (SPIONs) may serve as an effective, non‑invasive method for tracking transplanted cells in vivo. The present study provided direct evidence that hUC‑MSCs in the CIA rat model migrated to the inflammatory joint sites, effectively promoting recovery from collagen type II damage and thereby improving the immune‑associated prothrombotic state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Avian Proteins
  • Cell Movement
  • Cell Tracking
  • Cells, Cultured
  • Chickens
  • Collagen Type II
  • Cytokines / blood
  • Female
  • Hindlimb / pathology
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Avian Proteins
  • Collagen Type II
  • Cytokines