Cell source-dependent in vivo immunosuppressive properties of mesenchymal stem cells derived from the bone marrow and synovial fluid of minipigs

Exp Cell Res. 2015 May 1;333(2):273-288. doi: 10.1016/j.yexcr.2015.03.015. Epub 2015 Mar 27.

Abstract

The in vitro differentiation and immunosuppressive capacity of mesenchymal stem cells (MSCs) derived from synovial fluid (SF-MSCs) and bone marrow extract (BM-MSCs) in an isogenic background of minipigs were comparatively analyzed in a collagen-induced arthritis (CIA) mouse model of rheumatoid arthritis (RA). The proliferation capacity and expression of pluripotent transcription factors (Oct3/4 and Sox2) were significantly (P<0.05) higher in SF-MSCs than in BM-MSCs. The differentiation capacity of SF-MSCs into adipocytes, osteocytes and neurocytes was significantly (P<0.05) lower than that of BM-MSCs, and the differentiation capacity of SF-MSCs into chondrocytes was significantly (P<0.05) higher than that of BM-MSCs. Systemic injection of BM- and SF-MSCs significantly (P<0.05) ameliorated the clinical symptoms of CIA mice, with SF-MSCs having significantly (P<0.05) higher clinical and histopathological recovery scores than BM-MSCs. Furthermore, the immunosuppressive properties of SF-MSCs in CIA mice were associated with increased levels of the anti-inflammatory cytokine interleukin (IL)-10, and decreased levels of the pro-inflammatory cytokine IL-1β and osteoclast-related sRANKL. In conclusion, SF-MSCs exhibited eminent pluripotency and differentiation capacity into chondrocytes, addition to substantial in vivo immunosuppressive capacity by elevating IL-10 and reducing IL-1β levels in CIA mice.

Keywords: Differentiation; Immunomodulation; Mesenchymal stem cell; Rheumatoid arthritis; Synovial fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Bone Marrow / immunology
  • Bone Marrow Cells / physiology
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunosuppression Therapy
  • Immunotherapy
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / physiology*
  • Mice, Inbred DBA
  • Swine
  • Swine, Miniature
  • Synovial Fluid / cytology

Substances

  • Cytokines