Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria

Abstract

The etiopathogenesis of chronic spontaneous urticaria (CSU) is not fully elucidated, and almost 30–40% of patients are resistant to treatments; therefore, there is still a need for the development of new and effective treatments. This study aimed to develop experimental cellular therapy for CSU patients resistant to current treatment options. Autologous adipose tissue mesenchymal stem cells (MSC) were administered to 10 refractory CSU patients who were then followed up for six months. The efficacy of treatment was evaluated according to the weekly urticaria activity scores (UAS7) and drug use scores (DUS7). To observe the effect of treatment on immune cells, CD4+ T cell subsets were analyzed by flow cytometry, and the serum IFN-γ, TNF-α, IL2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17a, IL-21, IL-22, TGF-β1, PGE2, IDO and anti-FcεRI levels were measured using the Luminex and ELISA methods. The values obtained were compared with 10 control refractory CSU patients and five healthy controls. We found that the T cell subsets and inflammatory molecules were not affected by MSC treatment during the follow-up period. In control patients, a significant decrease was detected only at the Th2 subset, TGF-β1, PGE2, IDO and anti-FcεRI levels on the 14th day of treatment. The UAS7 and DUS7 values of the MSC-treated patients significantly decreased during the follow-up period, but in control patients, a significant but temporary decrease was seen. According to our findings, unlike conventional treatment, MSC therapy resulted in longer and more effective recovery. Our data indicate that MSCs may be an alternative and effective approach for treatment-resistant CSU patients.

Graphical Abstract

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Abbreviations

AHs:

Antihistamines

ANA:

Anti-nuclear antibody

Anti-TG:

Anti-thyroglobulin

Anti-TPO:

Anti-thyroid peroxidase

ASST:

Autologous serum skin test

BC:

Basophile cell

CSU:

Chronic spontaneous urticaria

DUS7:

Weekly drug use scores

EAACI:

The European Academy of Allergy and Clinical Immunology

EDF:

European Dermatology Forum

FcεRI:

High-affinity receptor for IgE

GA2LEN:

Global Allergy and Asthma European Network

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon gamma

Ig:

Immunoglobulin

IL:

Interleukin

MC:

Mast cell

MSC:

Mesenchymal stem cell

PGE2:

Prostaglandin E2

TGF-β1:

Transforming growth factor beta 1

TNF-α:

Tumor necrosis factor alpha

Treg:

Regulatory T cell

UAS7:

Weekly urticaria activity scores

WAO:

World Allergy Organization

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Acknowledgements

We thank Dr. Yusuf Metin Gelmez and Mr. Abdullah Yılmaz from Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Immunology for their valuable help in flow cytometry analyses.

Funding

The Scientific and Technological Research Council of Turkey (TUBITAK) financially supported this study with reference number 215 S 612.

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Contributions

RBÖÖ: Conceptualization, Methodology, Investigation, Resources, Data Curation, Writing - Original Draft, ATÖ: Conceptualization, Methodology, Formal analysis, Investigation, Visualization, Data Curation, Writing - Original Draft, CK: Conceptualization, Methodology, Resources, Supervision, Project administration, Funding acquisition, Writing - Review & Editing, EO: Methodology, Investigation, Supervision, Writing - Review & Editing, : Methodology, Formal analysis, Supervision, Writing - Review & Editing, HK: Methodology, Resources, Writing - Review & Editing, MKE: Methodology, Resources, Writing - Review & Editing, GD: Methodology, Formal analysis, Supervision, Writing - Review & Editing.

Corresponding author

Correspondence to Alper Tunga Özdemir.

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Conflict of Interest

Prof. Ercüment Ovalı is an employee of Acıbadem Labcell, Istanbul. The other authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

Clinical Trial Registration

The presented study was registered at the U.S. National Library of Medicine clinicaltrials.gov website (Registration no: NCT02824393 and URL. https://clinicaltrials.gov/ct2/show/NCT02824393).

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Özgül Özdemir, R.B., Özdemir, A.T., Kırmaz, C. et al. Mesenchymal Stem Cells: a Potential Treatment Approach for Refractory Chronic Spontaneous Urticaria. Stem Cell Rev and Rep (2020). https://doi.org/10.1007/s12015-020-10059-w

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Keywords

  • Chronic spontaneous urticaria
  • Mesenchymal stem cells
  • T helper cells
  • Autoimmunity
  • Immunomodulation