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ORIGINAL RESEARCH article
Front. Genet.
Sec. Stem Cell Research
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1516626
This article is part of the Research Topic Advancements in Stem Cell Differentiation and Disease Applications View all articles
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Background: Ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI) is typically self-limiting and capable of complete self-repair. However, in cases of moderate-to-severe IRI-AKI, patients may develop chronic kidney disease due to inadequate repair processes. At present, there is no definitive treatment for this issue.Prior research has indicated that human umbilical cord mesenchymal stem cells (hucMSCs) can facilitate renal repair. In this preclinical study, we explored the role and underlying mechanisms of exosomes derived from human umbilical cord MSC (hucMSC-Exos) in the repair of renal tubular epithelial cells following injury. The objective was to examine the impact of human umbilical cord MSC-derived exosomes (MSC-Exo) with high and low expression of B7-H1 on incomplete repair after IRI in mice.Objective: This study examines the differential effects of B7-H1 high -Exo and B7-H1 low -Exo in the context of renal IRI treatment.Methods: Using flow cell sorting methods, we successfully separated B7-H1 high -hucMSCs from B7-H1 low -hucMSCs. We then extracted Exo from both subpopulations and injected them into mice through the tail vein. Following this, we performed in vitro cellular experiments and RNA sequencing.In comparison to the sham-operated group, mice in the IRI group demonstrated elevated serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr), accompanied by a more pronounced degree of renal tissue damage. The administration of exosomes via the tail vein markedly accelerated the recovery of renal function in IRI mice, with the therapeutic effect being more pronounced in those treated with B7-H1 high -Exo. Moreover, B7-H1 high -Exo treatment demonstrated superior efficacy in inhibiting renal tubular cell apoptosis compared to B7-H1 low -Exo in hypoxic/reoxygenated HK-2 cells. RNA sequencing of renal tissues from mice treated with B7-H1 high -Exo and B7-H1 low -Exo revealed that B7-H1 high -Exo may enhance renal tissue and tubular function by down-regulating C3, thereby facilitating the repair of renal tissue and tubular epithelial cells.
Keywords: renal ischemia-reperfusion injury, Exosomes, B7-H1, cell sorting, C3
Received: 24 Oct 2024; Accepted: 11 Mar 2025.
Copyright: © 2025 He, Lv, Yao, Liu, Wang, Wan, Wang, Wang, Zhou and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xinghua Lv, Department of Day Surgery Center, the First Hospital of Lanzhou University, Lanzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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