Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling
Abstract Background 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. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine...
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-021-02547-8 |
| _version_ | 1818358195206225920 |
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| author | Nari Shin Namhee Jung Seung-Eun Lee Dasom Kong Nam Gyo Kim Myung Geun Kook Hwanhee Park Soon Won Choi Seunghee Lee Kyung-Sun Kang |
| author_facet | Nari Shin Namhee Jung Seung-Eun Lee Dasom Kong Nam Gyo Kim Myung Geun Kook Hwanhee Park Soon Won Choi Seunghee Lee Kyung-Sun Kang |
| author_sort | Nari Shin |
| collection | DOAJ |
| description | Abstract Background 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. 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. Methods hUCB-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. Results Pimecrolimus 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. Conclusions Coadministration 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. |
| first_indexed | 2024-12-13T20:25:08Z |
| format | Article |
| id | doaj.art-52f3d67bfed34dd0beeca6a4b2fe1840 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T20:25:08Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj.art-52f3d67bfed34dd0beeca6a4b2fe18402022-12-21T23:32:35ZengBMCStem Cell Research & Therapy1757-65122021-08-0112111610.1186/s13287-021-02547-8Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signalingNari Shin0Namhee Jung1Seung-Eun Lee2Dasom Kong3Nam Gyo Kim4Myung Geun Kook5Hwanhee Park6Soon Won Choi7Seunghee Lee8Kyung-Sun Kang9Adult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityStem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd., Ace Highend Tower 8Adult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityAdult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityAdult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityAdult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityStem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd., Ace Highend Tower 8Adult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityStem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co. Ltd., Ace Highend Tower 8Adult Stem Cell Research Center, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National UniversityAbstract Background 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. 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. Methods hUCB-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. Results Pimecrolimus 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. Conclusions Coadministration 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.https://doi.org/10.1186/s13287-021-02547-8Atopic dermatitisStem cell therapyCombination therapyCalcineurin inhibitorNFAT signalingCOX2-PGE2 axis |
| spellingShingle | Nari Shin Namhee Jung Seung-Eun Lee Dasom Kong Nam Gyo Kim Myung Geun Kook Hwanhee Park Soon Won Choi Seunghee Lee Kyung-Sun Kang Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling Stem Cell Research & Therapy Atopic dermatitis Stem cell therapy Combination therapy Calcineurin inhibitor NFAT signaling COX2-PGE2 axis |
| title | Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling |
| title_full | Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling |
| title_fullStr | Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling |
| title_full_unstemmed | Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling |
| title_short | Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling |
| title_sort | pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating nfat cox2 signaling |
| topic | Atopic dermatitis Stem cell therapy Combination therapy Calcineurin inhibitor NFAT signaling COX2-PGE2 axis |
| url | https://doi.org/10.1186/s13287-021-02547-8 |
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