Allergic diseases have become a global health problem and the most prevalent allergic disorders include allergic asthma, allergic skin diseases, allergic rhinitis, and allergic conjunctivitis. In the therapy of allergic diseases, corticosteroids, antihistamines, antileukotrienes and β2 adrenergic receptor agonists temporarily inhibit inflammation mediators and immune cells. However, long-term treatment causes various adverse effects. Drug resistance and intolerance also limit the application in some patients. Therefore, a new therapeutic method is urgently needed for allergic disease treatment.
Mesenchymal stem cells (MSCs) are multipotent, nonhematopoietic, stromal precursor cells found in adult and neonatal tissues. The most commonly used sources of MSCs are bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UCB-MSCs). These cells have tissue repair potential through their self-renewal and differentiation abilities and are increasingly considered regulators of immune responses. MSCs modulate the tissue repair process via differentiation into various types of cells, such as adipocytes, chondrocytes, osteocytes, tenocytes, fibroblasts, cardiomyocytes, skeletal myocytes, and neuronshepatocytes. MSCs contribute to the regeneration of damaged tissue resulting from several disease states, including cardiovascular disorders, liver damage,kidney injury, bone diseases and neurological defects. For immunomodulation function, MSCs exert an obviously suppressive effect on T cells, B cells, dendritic cells (DCs) and natural killer (NK) cells, affecting innate and adaptive immunity. Accumulating data have demonstrated that the action of MSCs on immune cells depends on the secretion of various factors, including tumor growth factor-β1 (TGF-β1), IL-10 and prostaglandin E2 (PGE2). The MSC secretome, especially extracellular vesicles (EVs), has exhibited therapeutic benefits in several animal models in recent years.
It is reasonable to speculate that these features make MSCs a potential therapeutic target for inflammatory diseases. Indeed, MSCs have been broadly administered with advantageous results in various autoimmune diseases, including systemic lupus erythematosus (SLE), graft-versus-host disease (GVHD), multiple sclerosis (MS) and rheumatoid arthritis (RA). Additionally, several researchers have found that MSCs are able to attenuate allergic immune diseases, including asthma, allergic rhinitis and allergic skin diseases (atopic dermatitis and allergic contact dermatitis), indicating that MSCs have an anti-inflammatory function and exert protective effects under different disease-specific inflammatory conditions. Therefore, all of these results suggest that MSC-based therapies could become potential treatments in immune-related diseases.
To understand the current status of MSCs in allergic diseases, we summarized the immunomodulatory properties of MSCs and critically analyzed their therapeutic potential in animal models and clinical trials of allergic asthma, allergic rhinitis, allergic skin diseases and allergic conjunctivitis in this review. We also highlight challenges that need to be overcome before MSC therapy can be used routinely to treat allergic diseases in the clinic.