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The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients

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Abstract

Introduction

Psoriasis cellular hallmarks, such as the imbalance between Th1/Th17 and Th2 cytokines and the dysregulated expression of vascular endothelial growth factor (VEGF), inducible nitric oxide synthase, (iNOS) and indoleamine 2,3-dioxygenase (IDO), are all detectable in mesenchymal stem cells (MSCs) suggesting that psoriasis originates at mesenchymal level. Aim of the study: In this scenario, MSCs may become the new therapeutic target and interest in the effects of traditionally used drugs, such as Apremilast, on MSCs has greatly increased.

Materials and Methods

MSCs from control subjects (C-MSCs) and from psoriatic patients before (PsO MSCs T0) and after in vivo treatment with Apremilast (PsO-MSCs T12) were isolated and characterized; subsequently, the effects of Apremilast on VEGF, iNOS and IDO expression were evaluated by immunocytochemistry (ICC). The expression of VEGF, iNOS and IDO was also detected in skin sections by immunohistochemistry (IHC).

Results

The results indicate that in vivo administration of Apremilast is able to drive the altered profile of PsO-MSCs towards a more physiological pattern. In skin sections, the role of Apremilast is evident in reducing VEGF, iNOS and IDO expression.

Conclusion

Apremilast treatment influences the expression of VEGF, iNOS and IDO not only by keratinocytes but also by MSCs, restoring their intrinsic profile and their natural anti-inflammatory action, and decreasing the auto-inflammatory process that underpins the development of psoriasis.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Clinical and Molecular Sciences, Dermatology Clinic, Università Politecnica delle Marche, Ancona, Italy

    Anna Campanati, Federico Diotallevi, Giulia Radi & Annamaria Offidani

  2. Department of Clinical and Molecular Sciences, Histology, Università Politecnica delle Marche, Via Tronto 10/A, 60126, Ancona, Italy

    Miriam Caffarini, Guendalina Lucarini, Mariangela Di Vincenzo & Monia Orciani

Authors
  1. Anna Campanati
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  2. Miriam Caffarini
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  3. Federico Diotallevi
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  4. Giulia Radi
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  5. Guendalina Lucarini
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  6. Mariangela Di Vincenzo
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  7. Monia Orciani
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Correspondence to Monia Orciani.

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All the authors declare that they have no conflict of interest.

Ethical approval

All procedures were performed in accordance with the ethical standards of the institutional research committee (Università Politecnica delle Marche Ethical Commitee (Protocol 2016 0360 OR) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Responsible Editor: J. Di Battista.

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Campanati, A., Caffarini, M., Diotallevi, F. et al. The efficacy of in vivo administration of Apremilast on mesenchymal stem cells derived from psoriatic patients. Inflamm. Res. 70, 79–87 (2021). https://doi.org/10.1007/s00011-020-01412-3

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  • DOI: https://doi.org/10.1007/s00011-020-01412-3

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