Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis via regulation of B lymphocyte maturation

Oncotarget. 2017 Jan 3;8(1):512-522. doi: 10.18632/oncotarget.13473.

Abstract

Mesenchymal stem cell (MSC) has been applied for the therapy of allergic disorders due to its beneficial immunomodulatory abilities. However, the underlying mechanisms for therapeutic efficacy are reported to be diverse according to the source of cell isolation or the route of administration. We sought to investigate the safety and the efficacy of human adipose tissue-derived MSCs (hAT-MSCs) in mouse atopic dermatitis (AD) model and to determine the distribution of cells after intravenous administration. Murine AD model was established by multiple treatment of Dermatophagoides farinae. AD mice were intravenously infused with hAT-MSCs and monitored for clinical symptoms. The administration of hAT-MSCs reduced the gross and histological signatures of AD, as well as serum IgE level. hAT-MSCs were mostly detected in lung and heart of mice within 3 days after administration and were hardly detectable at 2 weeks. All of mice administered with hAT-MSCs survived until sacrifice and did not demonstrate any adverse events. Co-culture experiments revealed that hAT-MSCs significantly inhibited the proliferation and the maturation of B lymphocytes via cyclooxygenase (COX)-2 signaling. Moreover, mast cell (MC) degranulation was suppressed by hAT-MSC. In conclusion, the intravenous infusion of hAT-MSCs can alleviate AD through the regulation of B cell function.

Keywords: B cell maturation; atopic dermatitis; distribution; mast cell degranulation; mesenchymal stem cells.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / physiology*
  • Cell Differentiation*
  • Cells, Cultured
  • Coculture Techniques
  • Cyclooxygenase 2 / metabolism
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / metabolism*
  • Dermatitis, Atopic / pathology
  • Dermatitis, Atopic / therapy
  • Disease Models, Animal
  • Humans
  • Male
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Transforming Growth Factor beta1
  • Cyclooxygenase 2