The Potential of Mesenchymal Stem Cells-Derived Exosome as a Novel Therapeutic Strategy for Atopic Dermatitis

Atopic dermatitis (AD) is one of the most popular chronic or recurrent inflammatory skin diseases affecting 15-20% of children and 2-5% of adults. Approximately 20% of patients with AD have moderate to severe forms of the disease, these severe refractory cases raise a difficult challenge for clinicians and patients. In the treatment of moderate-to-severe AD, topical corticosteroids and topical calcineurin inhibitors can be regularly prescribed. Patients with nonresponsive disease may need systemic immunosuppressants, phototherapy or anti-IL-4 receptor alpha-chain antibody. Although biologics that target a specific cytokine or mediator seem to be effective in some cases, the multifactorial background of AD explains the therapeutic failures in some cases and justifies the demand of new solutions. Mesenchymal stem cells (MSC)-mediated immunomodulation has been investigated in various inflammatory and allergic disorders, including several inflammatory skin processes. Considering the long-term risk of MSCs therapy remain uncertain, exosome that secreted by MSCs may be an excellent substitute. Exosomes are small vesicles that released into the extracellular space after the fusion of multivesicular bodies with the cell membrane. Exosomes contain proteins, mRNAs, miRNAs and can transfer molecules to recipient cell via membrane vesicle trafficking. Exosomes have shown strong therapeutic potential in many clinical diseases. Skin barrier dysfunction and immune dysregulation (inflammation) are two major characteristics of AD. Exosomes of stem cells have illustrated their modulatory potential for both keratinocytes and immune function. Therefore, the use of exosome-related treatment may be a novel therapeutic strategy for atopic dermatitis but it needs more validation. Our hypothesis is stem cells (SC) -derived exosome-related treatment modalities has potential as a novel therapeutic strategy for AD. We design a three-year project to explore the therapeutic effect of human SC-derived exosomes for AD.For the 1st year: We will 1. Isolate and verify exosomes from adipose tissue-derived mesenchymal stem cell (ADSC) and Wharton's jelly-derived mesenchymal stem cell (WJSC).2. Determine whether ADSC or WJSC derived exosomes are more effective in immune modulation and keratinocyte protection. For the 2nd year: based on the result of 1st year, we intend1. To compare the immuno-modulatory effects of corticosteroid, Tacrolimus, and candidate SC derived-exosomes on human T-cells (AD patients and health adults) by in vitro study.2. To compare the anti-apoptosis and anti-inflammatory effects of corticosteroid, Tacrolimus, and candidate SC derived-exosomes on human keratinocyte by in vitro study.3. To establish a suitable AD animal model. For the 3rd year: based on the result of 2nd year, we intend1. To investigate the clinical therapeutic effect and therapeutic mechanism of candidate SC derived-exosomes on a suitable AD rat model.2. To compare the therapeutic effect of corticosteroid, Tacrolimus and candidate SC derived-exosomes on AD rat model.Through this study, we can establish a platform to test the immune modulatory and keratinocytes protective effects of indicated SC-derived exosomes in comparison with current AD drugs. We can establish an AD animal model that provide important insights into the pathogenesis of skin barrier disruption and inflammation. We can also investigate the therapeutic potential of SC derived-exosomes for AD.

Project ID:PC10907-1103
External Project ID:MOST109-2314-B182-040