Xiao Tuo, Chen Yuhao, Jiang Bo, Huang Mengjie, Liang Yanjun, Xu Yue, Zheng Xumin, Wang Wenjuan, Chen Xiangmei, Cai Guangyan
Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing, 100853, China.
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Stem Cell Res Ther. 2025 Feb 28;16(1):102. doi: 10.1186/s13287-025-04137-4.
Acute kidney injury (AKI) is a major global public health concern with limited treatment options. While preclinical studies have suggested the potential of mesenchymal stem cells (MSCs) to repair and protect injured kidneys in AKI, clinical trials using transarterial MSCs transplantation have yielded disappointing results. This study aimed to investigate the feasibility and safety of minimally invasive renal subcapsular transplantation of MSCs for treating AKI in a minipig model, ultimately aiming to facilitate the clinical translation of this approach.
A novel AKI minipig model was established by combining cisplatin with hydration to evaluate the effectiveness of potential therapies. Renal subcapsular catheterization was successfully achieved under ultrasound guidance. Subsequently, the efficacy of renal subcapsular MSCs transplantation was assessed, and the biological role of the tryptophan metabolite kynurenine (Kyn) in AKI was elucidated through both in vivo and in vitro experiments.
The method of pre-hydration at 4% of body weight, followed by post-cisplatin (3.8 mg/kg) hydration at 2% of body weight, successfully established a cisplatin-induced AKI minipig model with a survival time exceeding 28 days, closely mimicking the clinical characteristics of typical AKI patients. Additionally, we discovered that multiple MSCs transplantations promoted renal function recovery more effectively than single transplantation via the renal subcapsular catheter. Furthermore, elevated levels of Kyn were observed in kidney during AKI, which activated the aryl hydrocarbon receptor (AhR)-mediated NF-κB/NLRP3/IL-1β signaling pathway in tubular epithelial cells, thereby exacerbating inflammatory injury.
Ultrasound-guided renal subcapsular transplantation of mesenchymal stem cells is a safe and effective therapeutic approach for AKI, with the potential to bring about significant clinical advancements in the future.
急性肾损伤（AKI）是一个重大的全球公共卫生问题，治疗选择有限。虽然临床前研究表明间充质干细胞（MSCs）具有修复和保护AKI中受损肾脏的潜力，但使用经动脉MSCs移植的临床试验结果令人失望。本研究旨在探讨在小型猪模型中进行MSCs微创肾被膜下移植治疗AKI的可行性和安全性，最终目的是推动该方法的临床转化。
通过顺铂与水化联合建立一种新型AKI小型猪模型，以评估潜在治疗方法的有效性。在超声引导下成功实现肾被膜下置管。随后，评估肾被膜下MSCs移植的疗效，并通过体内和体外实验阐明色氨酸代谢产物犬尿氨酸（Kyn）在AKI中的生物学作用。
先以体重4%进行预水化，然后以体重2%进行顺铂（3.8mg/kg）后水化的方法，成功建立了顺铂诱导的AKI小型猪模型，其存活时间超过28天，紧密模拟了典型AKI患者的临床特征。此外，我们发现多次MSCs移植比通过肾被膜下导管进行单次移植更有效地促进肾功能恢复。此外，在AKI期间肾脏中观察到Kyn水平升高，其激活了肾小管上皮细胞中芳烃受体（AhR）介导的NF-κB/NLRP3/IL-1β信号通路，从而加剧炎症损伤。
超声引导下间充质干细胞肾被膜下移植是一种治疗AKI的安全有效的治疗方法，未来有可能带来重大的临床进展。
