Benassi, L.

Kaleci, S.

Magnoni, C.

Paganelli, A.

Pellacani, G.

English

Paganelli A.

Kaleci S.

Benassi L.

Pellacani G.

Magnoni C.

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

L E T T E R T O TH E E D I T O RMesenchymal stem cells and psoriasis: State of the art andfuture perspectivesDear EditorMesenchymal stem cells (MSCs) are a subset of pluripotent cells presentin tissues of mesenchymal origin and responsible for their regeneration.MSCs include many different cell types, probably the most widely stud-ied being the bone marrow stromal stem cells (BMSCs). Other typesof MSCs are, for example, umbilical cord mesenchymal stem cells(UCMSCs), amniotic fluid stem cells (Amn-MSC), and adipose-derivedstem cells (ADSCs). MSCs are currently widely studied not only for theirregenerative capacity but also for their immunomodulating properties,thus giving reason to their use in clinical trials for autoimmune andautoinflammatory disorders. In this setting, several authors have investi-gated the role of MSCs as a possible therapeutic strategy for the treat-ment of psoriasis in both clinical and preclinical models.Previous studies already confirmed the involvement of MSCs in thepathogenesis of the disease and, therefore, designated MSCs asimportant potential therapeutic targets in the setting of psoriasis (Niu &Zhang, 2016). Liu and coworkers stated that lymphocyte inhibition iscompromised in psoriatic skin, mainly because of MSCs in psoriaticlesions leading to abnormalities in cytokine secretion (Liu, Yang, Yan, &Zhang, 2013). MSCs from skin lesions of psoriatic patients also promotekeratinocyte proliferation, resulting in abnormal thickening of the epi-dermis (Figure 1). Moreover, several papers reported on the central roleplayed by MSCs in response to biologic therapies: MSCs in fact seem tobe key players in mediating the pleiotropic effects of those drugs onboth keratinocytes and T cells. Campanati and coauthors in particulardemonstrated that the effects of TNF-alpha inhibitors take place at thelevel of dermal MSCs, which probably represent the cells primarilyinvolved in the “psoriatic march” (Campanati et al., 2017).To date, only few anecdotal reports of patients treated withMSC-based regimens have been published. A total of six patientsF IGURE 1 Schematicrepresentation of the role ofmesenchymal stem cell in psoriasis.Under physiological conditions, skin-resident T lymphocytes andLangerhans cells are in a quiescentstate and epithelial renewal is finelycontrolled. On the contrary, MSCdysfunction results in secretion ofproinflammatory cytokines and localrecruitment of activated Th1 andTh17 lymphocytes, responsible forthe hyperkeratosis, parakeratosis, andpapillomatosis typical of psoriaticplaques. Although therapies ofconventional immunosuppressantsfor psoriasis only act on lymphocytemodulation, biologic therapies have acombined action on both cytokineand MSC modulation. The aim ofMSC-based therapeutic regimens isto restore a physiologicalnondysfunctional MSC population(created with BioRender.com)Received: 3 January 2020 Revised: 25 January 2020 Accepted: 31 January 2020DOI: 10.1111/dth.13247Dermatologic Therapy. 2020;33:e13247. wileyonlinelibrary.com/journal/dth © 2020 Wiley Periodicals, Inc. 1 of 2https://doi.org/10.1111/dth.13247affected by psoriasis have been described in four clinical studies. Ofthem, two patients received intravenous injection of UCMSCs andthree of ADSCs, while only one patient was treated with topical appli-cation of ADSC-conditioned medium. So far, MSC-based therapiesproved their efficacy in all described cases (Chen et al., 2016).However, most of the research is today still limited to the benchside. Preclinical studies, mainly using imiquimod-induced murinemodels of psoriasis, have in fact recently stressed the potential thera-peutic efficacy of MSCs, with surprisingly promising results (Chenet al., 2019). However, no standardized experimental models are cur-rently available, since huge differences both in the type of MSC used(dermal MSCs, ADSCs, UCMSCs, and embryonic stem cell-derivedMSCs) and the administration route (intravenous, intralesional, andtopical) can be found in the literature. The effects of MSC administra-tion are certainly mediated by their well-known immunomodulatingaction on both T cells and dendritic cells through cytokine secretion.However, the possibility of a direct interaction between MSCs andkeratinocytes remains unknown and should be clarified. Anotherimportant point for future research is the possibility of obtaining effi-cient MSC from psoriatic patients: since dermal MSCs in psoriaticplaques have been shown to be altered, also other MSCs could beimpaired in terms of function and it is therefore imperative to checkwhether autologous MSCs can be efficiently used for psoriasistreatment.CONFLICTS OF INTERESTThe authors have no conflict of interest to declare.Alessia Paganelli1,2Shaniko Kaleci1Luisa Benassi1Giovanni Pellacani1Cristina Magnoni11Division of Dermatology, Surgical, Medical and Dental Department ofMorphological Sciences related to Transplant, Oncology and RegenerativeMedicine, Modena, Italy2Clinical and Experimental Medicine, University of Modena and ReggioEmilia, Modena, ItalyCorrespondenceAlessia Paganelli, MD, Via del Pozzo 71, 41124 Modena, Italy.Email: alessia.paganelli@gmail.com, +390594224264.ORCIDAlessia Paganelli https://orcid.org/0000-0002-0916-7769REFERENCESCampanati, A., Orciani, M., Lazzarini, R., Ganzetti, G., Consales, V.,Sorgentoni, G., … Offidani, A. (2017). TNF-α inhibitors reduce thepathological Th 1-Th 17/Th 2 imbalance in cutaneous Mesenchymalstem cells of psoriasis patients. Experimental Dermatology, 26(4),319–324. https://doi.org/10.1111/exd.13139Chen, H., Niu, J.-W., Ning, H.-M., Pan, X., Li, X.-B., Li, Y., … Zhang, B.(2016). Treatment of psoriasis with mesenchymal stem cells. The Amer-ican Journal of Medicine, 129(3), e13–e14. https://doi.org/10.1016/j.amjmed.2015.11.001Chen, Maosheng, Jing Peng, Qi Xie, Na Xiao, Xian Su, Hua Mei,Yeping Lu, et al. 2019. “Mesenchymal stem cells alleviatemoderate-to-severe psoriasis by reducing the production of type Iinterferon (IFN-I) by plasmacytoid dendritic cells (PDCs).” StemCells International 2019: 6961052. https://doi.org/10.1155/2019/6961052, 1, 13.Liu, R., Yang, Y., Yan, X., & Zhang, K. (2013). Abnormalities in cytokinesecretion from mesenchymal stem cells in psoriatic skin lesions.European Journal of Dermatology, 23(5), 600–607. https://doi.org/10.1684/ejd.2013.2149Niu, X., & Zhang, K. (2016). Dysregulated expression of inflammation-related genes in psoriatic dermis mesenchymal stem cells. ActaBiochimica et Biophysica Sinica, 48(6), 587–588. https://doi.org/10.1093/abbs/gmw0362 of 2 LETTER TO THE EDITOR

Mesenchymal stem cells and psoriasis: State of the art and future perspectives

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Mesenchymal stem cells and psoriasis: State of the art and future perspectives

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