Human Adipose Tissue-Derived Stromal Cells Ameliorate Adriamycin-Induced Nephropathy by Promoting Angiogenesis.

IF 1.6 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Organogenesis Pub Date : 2024-12-31 Epub Date: 2024-05-26 DOI:10.1080/15476278.2024.2356339
Xiaodi Zhao, Chengyan Ma, Lijie Li, Yuemei Yang, Sen Zhang, Xiaoli Wang
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Abstract

This study is to investigate the therapeutical effect and mechanisms of human-derived adipose mesenchymal stem cells (ADSC) in relieving adriamycin (ADR)-induced nephropathy (AN). SD rats were separated into normal group, ADR group, ADR+Losartan group (20 mg/kg), and ADR + ADSC group. AN rats were induced by intravenous injection with adriamycin (8 mg/kg), and 4 d later, ADSC (2 × 105 cells/mouse) were administrated twice with 2 weeks interval time (i.v.). The rats were euthanized after the 6 weeks' treatment. Biochemical indicators reflecting renal injury, such as blood urea nitrogen (BUN), neutrophil gelatinase alpha (NGAL), serum creatinine (Scr), inflammation, oxidative stress, and pro-fibrosis molecules, were evaluated. Results demonstrated that we obtained high qualified ADSCs for treatment determined by flow cytometry, and ADSCs treatment significantly ameliorated renal injuries in DN rats by decreasing BUN, Scr and NGAL in peripheral blood, as well as renal histopathological injuries, especially protecting the integrity of podocytes by immunofluorescence. Furthermore, ADSCs treatment also remarkably reduced the renal inflammation, oxidative stress, and fibrosis in DN rats. Preliminary mechanism study suggested that the ADSCs treatment significantly increased renal neovascularization via enhancing proangiogenic VEGF production. Pharmacodynamics study using in vivo imaging confirmed that ADSCs via intravenous injection could accumulate into the kidneys and be alive at least 2 weeks. In a conclusion, ADSC can significantly alleviate ADR-induced nephropathy, and mainly through reducing oxidative stress, inflammation and fibrosis, as well as enhancing VEGF production.

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人脂肪组织衍生基质细胞通过促进血管生成改善阿霉素诱发的肾病
本研究旨在探讨人源脂肪间充质干细胞(ADSC)对缓解阿霉素(ADR)诱导的肾病(AN)的治疗效果和机制。将SD大鼠分为正常组、ADR组、ADR+洛沙坦组(20 mg/kg)和ADR+ADSC组。通过静脉注射阿霉素(8 毫克/千克)诱导 AN 大鼠,4 天后注射 ADSC(2 × 105 个细胞/只小鼠)两次,每次间隔 2 周(静脉注射)。大鼠在治疗 6 周后安乐死。评估反映肾损伤的生化指标,如血尿素氮(BUN)、中性粒细胞明胶酶α(NGAL)、血清肌酐(Scr)、炎症、氧化应激和促纤维化分子。结果表明,通过流式细胞仪测定,我们获得了高质量的 ADSCs 用于治疗,ADSCs 治疗显著改善了 DN 大鼠的肾损伤,降低了外周血中的 BUN、Scr 和 NGAL,也减轻了肾组织病理学损伤,尤其是通过免疫荧光检测保护了荚膜细胞的完整性。此外,ADSCs 治疗还显著减轻了 DN 大鼠的肾脏炎症、氧化应激和纤维化。初步机理研究表明,ADSCs 治疗可通过促进血管内皮生长因子(VEGF)的产生,显著增加肾脏新生血管。利用体内成像技术进行的药效学研究证实,ADSCs 经静脉注射可在肾脏内蓄积并存活至少 2 周。总之,ADSC 能显著缓解 ADR 引起的肾病,主要是通过减少氧化应激、炎症和纤维化,以及促进血管内皮生长因子的产生。
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来源期刊
Organogenesis
Organogenesis BIOCHEMISTRY & MOLECULAR BIOLOGY-DEVELOPMENTAL BIOLOGY
CiteScore
4.10
自引率
4.30%
发文量
6
审稿时长
>12 weeks
期刊介绍: Organogenesis is a peer-reviewed journal, available in print and online, that publishes significant advances on all aspects of organ development. The journal covers organogenesis in all multi-cellular organisms and also includes research into tissue engineering, artificial organs and organ substitutes. The overriding criteria for publication in Organogenesis are originality, scientific merit and general interest. The audience of the journal consists primarily of researchers and advanced students of anatomy, developmental biology and tissue engineering. The emphasis of the journal is on experimental papers (full-length and brief communications), but it will also publish reviews, hypotheses and commentaries. The Editors encourage the submission of addenda, which are essentially auto-commentaries on significant research recently published elsewhere with additional insights, new interpretations or speculations on a relevant topic. If you have interesting data or an original hypothesis about organ development or artificial organs, please send a pre-submission inquiry to the Editor-in-Chief. You will normally receive a reply within days. All manuscripts will be subjected to peer review, and accepted manuscripts will be posted to the electronic site of the journal immediately and will appear in print at the earliest opportunity thereafter.
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