Nardozi Daniela, Palumbo Stefania, Khan Arif Ul Maula, Sticht Carsten, Bieback Karen, Sadeghi Samar, Kluth Mark Andreas, Keese Michael, Gretz Norbert
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany.
Vascular Surgery, University Hospital Mannheim, 68167 Mannheim, Germany.
J Clin Med. 2022 May 5;11(9):2601. doi: 10.3390/jcm11092601.
Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5 stromal cells (2 × 10) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5 and ASC-treated groups. Additionally, ABCB5 and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD.
多囊肾病（CKD）是一组异质性的遗传疾病，也是终末期肾病最常见的病因之一。在此，我们研究长期人类干细胞治疗对PKD/Mhm（Cy/+）大鼠肾功能和基因表达谱的潜在影响。人脂肪来源的基质细胞（ASC）和人皮肤来源的ABCB5基质细胞（2×10）在6个月内每月通过静脉或腹腔内注射。此外，腹腔内给予ASC和ABCB5来源的条件培养基。基因表达谱结果显示，代谢相关途径发生了显著的重编程，同时cAMP、NF-κB和凋亡途径下调。在实验期间，我们使用一种创新的非侵入性经皮装置测量了主要的肾脏参数以及肾功能。总体而言，这些分析表明ABCB5和ASC治疗组的肾功能有适度改善。此外，ABCB5和ASC来源的条件培养基治疗导致的改善较轻微但仍有前景。尽管还需要进行进一步分析，但本研究获得的初步结果可为在CKD中应用基于细胞的治疗的新型治疗方法奠定基础。
