hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model

Abstract

Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.

Metadata

Authors/Creators:	Xu, H. https://orcid.org/0009-0004-3242-4550 Jiang, W. https://orcid.org/0000-0002-8315-339X Li, X. https://orcid.org/0000-0002-2925-5088 Jiang, J. https://orcid.org/0009-0009-5464-7057 Afridi, S.K. https://orcid.org/0000-0003-1633-4470 Deng, L. https://orcid.org/0009-0002-5881-5598 Li, R. https://orcid.org/0000-0002-1932-3737 Luo, E. Zhang, Z. Huang, Y.-W.A. https://orcid.org/0000-0003-4082-8008 Cui, Y. https://orcid.org/0000-0002-3063-0324 So, K.-F. https://orcid.org/0000-0003-4039-4246 Chen, H. https://orcid.org/0009-0000-5631-9713 Qiu, W. https://orcid.org/0000-0002-0880-958X Tang, C. https://orcid.org/0000-0001-7048-108X
Copyright, Publisher and Additional Information:	This item is protected by copyright. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 9 January 2024 Published (online): 20 January 2024 Published: 20 January 2024
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	25 Jan 2024 16:23
Last Modified:	25 Jan 2024 16:23
Status:	Published
Publisher:	Nature Research
Identification Number:	https://doi.org/10.1038/s41536-024-00349-z
Related URLs:	PubMed URL

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hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model

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