Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model

Clin Exp Allergy. 2017 Jul;47(7):937-945. doi: 10.1111/cea.12920. Epub 2017 May 11.

Abstract

Background: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma.

Objective: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model.

Methods: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells.

Results: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs.

Conclusions: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Keywords: animal models; asthma; clinical immunology; mesenchymal stem cell; mice; umbilical cord.

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / immunology*
  • Asthma / metabolism*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Fetal Blood / cytology*
  • Humans
  • Immunization
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunomodulation*
  • Inflammation Mediators / metabolism
  • Lymph Nodes / immunology
  • Mesenchymal Stem Cells / metabolism*
  • Methacholine Chloride / metabolism
  • Mice
  • Ovalbumin / immunology*
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Allergens
  • Cytokines
  • Inflammation Mediators
  • Methacholine Chloride
  • Immunoglobulin E
  • Ovalbumin