Abstract
BackgroundHuman mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine AD model by inhibiting the activation of mast cells and B cells. Also our phase I/IIa clinical trial showed clinical efficacy and safety of hMSCs in moderate-to-severe adult AD patients. However, hMSCs therapy against atopic dermatitis have had poor results in clinical field. Therefore, we investigated the reason behind this result. We hypothesized that drug–cell interaction could interfere with the therapeutic efficacy of stem cells, and investigated whether coadministration with pimecrolimus, one of the topical calcineurin inhibitors, could influence the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in AD.MethodshUCB-MSCs were subcutaneously injected to AD-induced mice with or without pimecrolimus topical application. To examine whether pimecrolimus influenced the immunomodulatory activity of hUCB-MSCs, hUCB-MSCs were treated with pimecrolimus.ResultsPimecrolimus disturbed the therapeutic effect of hUCB-MSCs when they were co-administered in murine AD model. Moreover, the inhibitory functions of hUCB-MSCs against type 2 helper T (Th2) cell differentiation and mast cell activation were also deteriorated by pimecrolimus treatment. Interestingly, we found that pimecrolimus decreased the production of PGE2, one of the most critical immunomodulatory factors in hUCB-MSCs. And we demonstrated that pimecrolimus downregulated COX2-PGE2 axis by inhibiting nuclear translocation of NFAT3.ConclusionsCoadministration of pimecrolimus with hMSCs could interfere with the therapeutic efficacy of hMSCs in atopic dermatitis, and this is the first study that figured out the interaction of hMSCs with other drugs in cell therapy of atopic dermatitis. Therefore, this study might give rise to improvement of the clinical application of hMSCs therapy and facilitate the widespread application of hMSCs in clinical field.
Highlights
Human mesenchymal stem cells therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability
We investigated whether the combined application of Human mesenchymal stem cells (hMSCs) and calcineurin inhibitors limits the therapeutic effect of cell therapy in subjects with AD
Combined administration of hUCB‐mesenchymal stem cell (MSC) with pimecrolimus adversely affects the therapeutic potential of hUCB‐MSCs against AD mouse model As a calcineurin inhibitor, pimecrolimus is one of the most common anti-inflammatory drugs used to treat AD
Summary
Human mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. Atopic dermatitis (AD) is a chronic and relapsing skin disorder characterized by eczematous skin lesions with severe pruritus and epidermal barrier dysfunction [1]. The pathogenesis of AD is characterized by excessive type 2 helper T (Th2) cell-mediated inflammation, resulting in increased serum levels of total IgE and skin barrier dysfunction. Calcineurin inhibitors are one of the most common medications prescribed for patients with AD [4,5,6] These drugs bind to FK506binding protein-12 (FKBP-12), inhibit the serine/threonine phosphatase calcineurin, and subsequently prevent nuclear translocation of nuclear factor of activated T cells (NFAT). NFAT-mediated transcription of proinflammatory cytokines in T cells is suppressed [7] These classical drugs are insufficient to resolve severe AD or exert significant undesirable side effects [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
