Human Wharton's Jelly-Derived Stem Cells Display Immunomodulatory Properties and Transiently Improve Rat Experimental Autoimmune Encephalomyelitis

Cell Transplant. 2015;24(10):2077-98. doi: 10.3727/096368914X685104. Epub 2014 Oct 10.


Umbilical cord matrix or Wharton's jelly-derived stromal cells (WJ-MSCs) are an easily accessible source of mesenchymal-like stem cells. Recent studies describe a hypoimmunogenic phenotype, multipotent differentiation potential, and trophic support function for WJ-MSCs, with variable clinical benefit in degenerative disease models such as stroke, myocardial infarction, and Parkinson's disease. It remains unclear whether WJ-MSCs have therapeutic value for multiple sclerosis (MS), where autoimmune-mediated demyelination and neurodegeneration need to be halted. In this study, we investigated whether WJ-MSCs possess the required properties to effectively and durably reverse these pathological hallmarks and whether they survive in an inflammatory environment after transplantation. WJ-MSCs displayed a lowly immunogenic phenotype and showed intrinsic expression of neurotrophic factors and a variety of anti-inflammatory molecules. Furthermore, they dose-dependently suppressed proliferation of activated T cells using contact-dependent and paracrine mechanisms. Indoleamine 2,3-dioxygenase 1 was identified as one of the main effector molecules responsible for the observed T-cell suppression. The immune-modulatory phenotype of WJ-MSCs was further enhanced after proinflammatory cytokine treatment in vitro (licensing). In addition to their effect on adaptive immunity, WJ-MSCs interfered with dendritic cell differentiation and maturation, thus directly affecting antigen presentation and therefore T-cell priming. Systemically infused WJ-MSCs potently but transiently ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model for MS, when injected at onset or during chronic disease. This protective effect was paralleled with a reduction in autoantigen-induced T-cell proliferation, confirming their immunomodulatory activity in vivo. Surprisingly, in vitro licensed WJ-MSCs did not ameliorate EAE, indicative of a fast rejection as a result of enhanced immunogenicity. Collectively, we show that WJ-MSCs have trophic support properties and effectively modulate immune cell functioning both in vitro and in the EAE model, suggesting WJ-MSC may hold promise for MS therapy. Future research is needed to optimize survival of stem cells and enhance clinical durability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Differentiation / physiology*
  • Cell Proliferation / physiology
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Humans
  • Lymphocyte Activation / immunology*
  • Mesenchymal Stem Cells / cytology*
  • Rats
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Umbilical Cord / cytology
  • Wharton Jelly / cytology*


  • Cytokines