Mesenchymal Stem Cells and Atopic Dermatitis: A Review

Abstract

Mesenchymal stem/stromal cells (MSCs) are stromal-derived non-hematopoietic progenitor cells that reside in and can be expanded from various tissues sources of adult and neonatal origin, such as the bone marrow, umbilical cord, umbilical cord blood, adipose tissue, amniotic fluid, placenta, dental pulp and skin. The discovery of the immunosuppressing action of MSCs on T cells has opened new perspectives for their use as a therapeutic agent for immune-mediated disorders, including allergies. Atopic dermatitis (AD), a chronic and relapsing skin disorder that affects up to 20% of children and up to 3% of adults worldwide, is characterized by pruritic eczematous lesions, impaired cutaneous barrier function, Th2 type immune hyperactivation and, frequently, elevation of serum immunoglobulin E levels. Although, in the dermatology field, the application of MSCs as a therapeutic agent was initiated using the concept of cell replacement for skin defects and wound healing, accumulating evidence have shown that MSC-mediated immunomodulation can be applicable to the treatment of inflammatory/allergic skin disorders. Here we reviewed the pre-clinical and clinical studies and possible biological mechanisms of MSCs as a therapeutic tool for the treatment of atopic dermatitis.

Keywords: atopic dermatitis; atopic eczema; immunomodulation; inflammatory skin diseases; mesenchymal stem/stromal cells.

FIGURE 1

Skin barrier dysfunction undergoing sensitization in AD. Allergens penetrating the skin (A) can be captured by Langerhans cells, which migrate to a regional draining lymph nodes (B,C). Langerhans cells present the allergen to a naïve T cells, causing polarization to a Th-2 phenotype which secrete cytokines, such as IL-4 and IL-13 (D), that stimulate B cells to become plasma cells and secrete allergen-specific IgE (E,F).

FIGURE 2

Immune responses involved in chronification of lesions in AD. Scratching resulting from pruritus (the main symptom of AD), makes keratinocytes react by releasing cytokines important for inflammation, including TSLP (thymic stromal lymphopoetin), IL-33, and IL-25. IL-33 activates innate lymphoid cells 2 (ILC2) and Th2 lymphocytes. The release of IL-31 stimulates even more the pruritus. In response to IL-22, keratinocytes proliferate, resulting in diffuse epidermal hyperplasia. Eosinophils accumulate in chronic atopic skin. MC: mast cells; LC: Langerhans cells; ILC2: Innate lymphoid cell 2.