CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice

Stem Cell Res Ther. 2016 Feb 3:7:23. doi: 10.1186/s13287-016-0285-4.

Abstract

Background: The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146(+) and CD146(-) MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated.

Methods: Flow cytometry was used to quantify IL-6 and TGF-β1 expressed on CD146(+) and CD146(-) MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA).

Results: Compared with CD146(-) MSCs, CD146(+) MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146(-) cells but not when exposed to CD146(+) cells both in vitro and in vivo. IA injection of CD146(+) MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A(+) CD146(+) cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression.

Conclusions: This study suggests that CD146(+) cells have greater potency than CD146(-) cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146(+) cells in treating inflammatory arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Experimental / therapy*
  • CD146 Antigen / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Humans
  • Immunomodulation
  • Interleukin-6 / physiology
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / immunology
  • Transforming Growth Factor beta / physiology

Substances

  • CD146 Antigen
  • Interleukin-6
  • MCAM protein, human
  • Transforming Growth Factor beta