Description |
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterised by intense itching and recurrent eczematous lesions. Although it most often starts in infancy and affects two of ten children, it is also highly prevalent in adults. It is the leading non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial burden on patients and their relatives, and increases the risk of food allergy, asthma, allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders. Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2 response and exaggerated IgE responses to allergens, it is now recognised as a lifelong disposition with variable clinical manifestations and expressivity, in which defects of the epidermal barrier are central. Present prevention and treatment focus on restoration of epidermal barrier function, which is best achieved through the use of emollients. Topical corticosteroids are still the first-line therapy for acute flares, but they are also used proactively along with topical calcineurin inhibitors to maintain remission.
Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers.
Induced pluripotent stem cells (iPSCs) are pluripotent stem cells generated from adult cells by reprogramming. iPSCs have the same properties as embryonic stem cells, and therefore self-renew and can differentiate into all cell types of the body except for cells in extra-embryonic tissues such as the placenta. iPSC-derived exosomes contain TGF- β、 BDNF etc., which can inhibit cell apoptosis, inhibit inflammatory response, promote angiogenesis, inhibit fibrosis, and enhance tissue repair potential, with a wide range of potential applications. iPSC-derived exosomes have emerged as an important paracrine factor for iPSCs to repair injured cells through the delivery of bioactive components.
The purpose of this trial is to evaluate the safety, tolerability, and preliminary efficacy of iPSC-derived exosomes in the treatment of atopic dermatitis. |