3D Biofabricated Immunocompetent Skin Tissue Model of Atopic Dermatitis for Testing the Efficacy of Immunomodulatory Mesenchymal Stromal Cell Therapies

FARE Award Winner

Authors

• X-X Nguy·ªÖn
• H Zarkoob
• MJ Song
• K Sung
• M Ferrer

Abstract

Atopic dermatitis (AD) is a complex inflammatory skin disease that involves multiple cell types and immune system imbalance. During disease progression, T-helper type 2 (Th2) cells migrate to the skin and secrete pro-inflammatory cytokines such as IL-4 and IL-13, which induce AD pathology in the skin. We have established a robust protocol to fabricate normal full thickness skin (FTS) and vascularized (VFTS) and AD-like FTS and VFTS tissues by treatment with IL-4. The IL-4 induced AD skin models recapitulate the hallmarks of AD including spongiosis-like intercellular spaces, epithelial hyperplasia, and the loss of barrier function, further highlighting the rescue of AD-like phenotypes by Tofacitinib, a potent inhibitor of the JAK-STAT pathways. Furthermore, in place of adding IL-4, we have increased the physiological complexity of the previous model by incorporating Th2 cells to induce the AD-phenotype. Our data show that Th2-incorporated skin tissues exhibit AD-like phenotypes including the loss of barrier function, suggesting the barrier function of the skin is impaired, and undifferentiated epidermal keratinocytes by histology. We also utilize our immunocompetent AD model test whether cell-based immunological therapies, such as mesenchymal stromal cells (MSC), can be used to monitor the suppressive T-cells response in the model, and additional MSC treatment helps to restore the vasculature formation in the AD model. Taken together, our 3D fabricated tissue models have potential to improve understanding of immune cell interactions and mechanisms during the initiation and progression of AD, while also providing testing platforms for different therapeutic approaches, including small molecules and biologics.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Monday, September 25, 2023