TNFα promotes proliferation of human synovial MSCs while maintaining chondrogenic potential

PLoS One. 2017 May 18;12(5):e0177771. doi: 10.1371/journal.pone.0177771. eCollection 2017.

Abstract

Synovial mesenchymal stem cells (MSCs) are a candidate cell source for cartilage and meniscus regeneration. If we can proliferate synovial MSCs more effectively, we can expand clinical applications to patients with large cartilage and meniscus lesions. TNFα is a pleiotropic cytokine that can affect the growth and differentiation of cells in the body. The purpose of this study was to examine the effect of TNFα on proliferation, chondrogenesis, and other properties of human synovial MSCs. Passage 1 human synovial MSCs from 2 donors were cultured with 2.5 x 10-12~10-7 g/ml, 10 fold dilution series of TNFα for 14 days, then the cell number and colony number was counted. The effect of the optimum dose of TNFα on proliferation was also examined in synovial MSCs from 6 donors. Chondrogenic potential of synovial MSCs pretreated with TNFα was evaluated in 6 donors. The expressions of 12 surface antigens were also examined in 3 donors.2.5 ng/ml and higher concentration of TNFα significantly increased cell number/dish and cell number/colony in both donors. The effect of 25 ng/ml TNFα was confirmed in all 6 donors. There was no significant difference in the weight, or amount of glycosaminoglycan and DNA of the cartilage pellets between the MSCs untreated and MSCs pretreated with 25 ng/ml TNFα. TNFα decreased expression rate of CD 105 and 140b in all 3 donors. TNFα promoted proliferation of synovial MSCs with increase of cell number/ colony. Pretreatment with TNFα did not affect chondrogenesis of synovial MSCs. However, TNFα affected some properties of synovial MSCs.

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Chondrogenesis / drug effects*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects*
  • Synovial Fluid / cytology*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported by JSPS KAKENHI grant number JP16K20039, Japan Agency for Medical Research and Development #122011A182, and Japan Society for the promotion of Science #15K10464. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.