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Article

Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders

1
Exogenus Therapeutics, S.A., 3060-197 Cantanhede, Portugal
2
Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
3
CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
4
IIIUC—Institute of Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Int. J. Mol. Sci. 2021, 22(18), 9797; https://doi.org/10.3390/ijms22189797
Received: 6 August 2021 / Revised: 26 August 2021 / Accepted: 6 September 2021 / Published: 10 September 2021
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism 2.0)
Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis. View Full-Text
Keywords: extracellular vesicles; EV; umbilical cord blood; inflammatory skin disease; psoriasis extracellular vesicles; EV; umbilical cord blood; inflammatory skin disease; psoriasis
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MDPI and ACS Style

Rodrigues, S.C.; Cardoso, R.M.S.; Freire, P.C.; Gomes, C.F.; Duarte, F.V.; Neves, R.P.d.; Simões-Correia, J. Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders. Int. J. Mol. Sci. 2021, 22, 9797. https://doi.org/10.3390/ijms22189797

AMA Style

Rodrigues SC, Cardoso RMS, Freire PC, Gomes CF, Duarte FV, Neves RPd, Simões-Correia J. Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders. International Journal of Molecular Sciences. 2021; 22(18):9797. https://doi.org/10.3390/ijms22189797

Chicago/Turabian Style

Rodrigues, Sílvia C., Renato M.S. Cardoso, Patricia C. Freire, Cláudia F. Gomes, Filipe V. Duarte, Ricardo P.d. Neves, and Joana Simões-Correia. 2021. "Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders" International Journal of Molecular Sciences 22, no. 18: 9797. https://doi.org/10.3390/ijms22189797

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