患者尿源性干细胞通过cxcl14依赖性调节巨噬细胞极化来缓解狼疮性肾炎

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-04-09 DOI:10.1016/j.lfs.2025.123623

Yunfei Xia , Yanju Zhang , Juan Ji , Guijuan Feng , Tianxing Chen , Haitao Li , Fengyan Zhou , Yanfeng Bao , Xuhui Zeng , Zhifeng Gu

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引用次数: 0

摘要

目的间充质干细胞（MSC）在狼疮性肾炎（LN）的治疗中显示出有希望的治疗潜力。然而，大多数间充质干细胞是侵入性的，只有同种异体间充质干细胞的移植才起作用。尿源性干细胞（USC）可以通过无创和安全的途径获得。USC是否可以用于自体干细胞移植治疗LN尚不清楚。材料和方法susc采集自健康个体、系统性红斑狼疮（SLE）无LN （NLN）患者和LN患者。比较了3种USC的生物学特性和免疫调节能力。观察USC对MRL/lpr小鼠LN的治疗价值及对巨噬细胞的影响。我们进一步探讨LN患者USC （LN-USC）对巨噬细胞极化的影响机制。主要发现：sln - usc细胞增殖更快，细胞凋亡更少，显著上调调节性T细胞（Treg），下调抗体分泌细胞（ASC）。重要的是，在三种USC类型中，LN-USC对MRL/lpr小鼠LN的作用最好。此外，当注射到MRL/lpr小鼠或与人急性单核细胞白血病细胞（THP1）来源的M0巨噬细胞共培养时，LN-USC显著下调巨噬细胞的M1极化。此外，敲低LN- usc的C-X-C基序趋化因子配体14 （CXCL14）后，对巨噬细胞极化的调节作用和对LN的治疗效果发生逆转。这些结果表明，移植LN-USC通过cxcl14依赖的方式抑制巨噬细胞的M1极化，减轻了MRL/lpr小鼠的LN，表明USC可作为LN自体干细胞治疗的潜在候选物。

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Urine-derived stem cells from patients alleviate lupus nephritis via regulating macrophage polarization in a CXCL14-dependent manner

Aim

Mesenchymal stem cells (MSC) exhibit hopeful therapeutic potential for the treatment of lupus nephritis (LN). Nevertheless, most MSC are harvested invasively and only transplantation of allogeneic MSC takes effect. Urine-derived stem cells (USC) can be obtained by noninvasive and safe access. Whether USC can be used for autologous stem cell transplantation to treat LN remains unknown.

Materials and methods

USC were harvested from healthy individuals, systemic lupus erythematosus (SLE) patients with no LN (NLN) and LN patients. The biological characteristics and immunomodulatory ability of three USC types were compared. Therapeutic value of USC for LN in MRL/lpr mice and influence of USC on macrophages were assessed. We further explored the mechanism of USC from LN patients (LN-USC) on macrophage polarization.

Key findings

LN-USC exhibited faster proliferation and less apoptosis, significantly upregulated regulatory T cells (Treg) and downregulated antibody secreting cells (ASC). Importantly, LN-USC showed the best effect on LN in MRL/lpr mice among the three USC types. Additionally, LN-USC markedly downregulated M1 polarization of macrophages when injected into MRL/lpr mice or co-cultured with human acute monocytic leukemia cell (THP1)-derived M0 macrophages. Moreover, the regulative effect on macrophage polarization and therapeutic efficacy on LN were reversed after knocking down C-X-C motif chemokine ligand 14 (CXCL14) of LN-USC.

Significance

These results suggested that transplantation of LN-USC alleviated LN in MRL/lpr mice via inhibiting M1 polarization of macrophages in a CXCL14-dependent manner, indicating that USC serve as a prospective candidate for autologous stem cell therapy of LN.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.