Fibroblasts as an Alternative to Mesenchymal Stem Cells with Successful Treatment and Immune Modulation in EAE Model of Multiple Sclerosis

The immune modulatory potential of mesenchymal stem cells (MSCs) is well known and is the basis for multiple clinical trials in treatment of autoimmune conditions. Unfortunately, MSCs are relatively rare, difficult to expand in culture, and methods of obtaining MSCs are complicated and expensive. In contrast, fibroblasts are found in copious amounts in various tissues, are a robust cellular population, and can be cultured without need for costs associated with culture media. Previous studies by our group and others have demonstrated fibroblasts possess regenerative activities. In the current study we demonstrated: a) fibroblasts inhibit mixed lymphocyte reaction; b) suppress T cell activation; c) inhibit DC maturation; and d) stimulate T regulatory (Treg) cell formation. Importantly, administration of fibroblasts in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis resulted in disease inhibition, which was abrogated upon depletion of Treg cells. This data, combined with existing clinical safety data on fibroblast administration, supports the clinical translation of fibroblast-based therapies for multiple sclerosis.