Mesenchymal stem/stromal cell therapy in atopic dermatitis and chronic urticaria: immunological and clinical viewpoints

Abstract

Allergic diseases are immune-mediated diseases. Allergies share a common immunopathogenesis, with specific differences according to the specific disease. Mesenchymal stem/stromal cells (MSCs) have been applied to people suffering from allergic and many other diseases. In this review, the immunologic roles of MSCs are systemically reviewed according to disease immunopathogenesis from a clinical viewpoint. MSCs seem to be a promising therapeutic modality not only as symptomatic treatments but also as causative and even preventive treatments for allergic diseases, including atopic dermatitis and chronic urticaria.

Keywords: Allergy; Atopic dermatitis; Chronic urticaria; Clinical viewpoint; Mesenchymal stem/stromal cell.

Fig. 1

The structure of the immunopathogenesis of allergic diseases. First, allergen-specific IgE and/or allergen-specific Th2 cell responses manifest through the sensitization phase. Thereafter, the clinical manifestations develop by allergy provocation through rechallenge with sensitized allergens. The classical pathway of immunopathogenesis of IgE-mediated allergy consists of allergen-IgE-FcεR1 binding on mast cells, followed by histamine release. Finally, histamine provokes allergic symptoms and signs, including urticaria, dyspnoea and even anaphylaxis. Additionally, there is an allergen-specific Th2 cell-mediated pathway that is important in eosinophilic inflammation in atopic dermatitis. Classically, many allergic diseases are allergen-specific. In chronic urticaria, autoimmune mechanisms play a role as an alternative pathway of immunopathogenesis and are not allergen-specific. Anaphylaxis due to drug allergies is a systemic disease, whereas allergic rhinitis and allergic conjunctivitis are generally limited to the nose and eyes. Allergic diseases present as local or systemic diseases

Fig. 2

Timeline of landmarks in the development of mesenchymal stem cells and their therapeutic application to allergic diseases

Fig. 3

Possible immunologic roles of MSCs by which therapeutic effects were expected and proven in AD. The numbers marked with asterisks (*) represent the immunologic mechanisms of MSCs in Table 1. Red arrows represent negative regulation, and blue arrows represent positive regulation. Blue text represents the flow of immunopathogenesis. The immunologic roles of MSCs are presented in black text for animal models of allergic conditions other than AD, green text for animal models of AD, and red text for human clinical trials

Fig. 4

Possible immunologic roles of MSCs by which therapeutic effects were expected to occur in animal models of allergic diseases other than CU. Blue text represents the flow of immunopathogenesis of CU, and black text represents the role of MSCs in allergic diseases