Department of Nephrology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Nephrology, Nanjing Drum Tower Hospital, The Affliated Hospital of Nanjing University Medical School, Nanjing, China.
Nephron. 2023;147(6):362-372. doi: 10.1159/000528812. Epub 2023 Jan 17.
Obtaining sufficient renal tubular epithelial cells (RTCs) and maintaining the functions of RTCs are vital for developing a bioartificial renal tubule-assisted device for continuous renal replacement therapy.
We established an optimal Transwell coculture system using human primary renal proximal tubule epithelial cells (RPTECs) and bone marrow mesenchymal stem cells at different cell ratios to investigate morphological and functional changes in RTCs. Changes in cell proliferation, megalin expression, cell cycle, apoptosis, and levels of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-7 (BMP-7) after cell culture were investigated.
RPTEC/BMMSC coculture at a cell ratio of 3:1 resulted in optimal morphology, function, and growth of RPTECs, in which, viability, proliferation, cytochrome P450 activity, and megalin expression in RPTECs were significantly increased compared to those in other cocultures or RPTECs alone. Additionally, IGF-1 and BMP-7 levels were significantly higher in the 3:1 RPTEC/BMMSC coculture than in the RPTECs alone.
Our results demonstrate that coculture with RPTECs has great potential for use in renal replacement therapy, thereby providing fundamental information for manufacturing a bioartificial kidney.
获取足够的肾小管上皮细胞（RTCs）并维持 RTCs 的功能对于开发用于连续肾脏替代治疗的生物人工肾小管辅助装置至关重要。
我们使用人原代近端肾小管上皮细胞（RPTECs）和骨髓间充质干细胞以不同的细胞比例建立了最佳的 Transwell 共培养系统，以研究 RTCs 的形态和功能变化。研究了细胞培养后细胞增殖、megalin 表达、细胞周期、细胞凋亡以及胰岛素样生长因子-1（IGF-1）和骨形态发生蛋白-7（BMP-7）水平的变化。
RPTEC/BMMSC 以 3:1 的细胞比例共培养可使 RPTECs 的形态、功能和生长达到最佳状态，其中 RPTECs 的活力、增殖、细胞色素 P450 活性和 megalin 表达明显高于其他共培养物或单独的 RPTECs。此外，3:1 的 RPTEC/BMMSC 共培养物中的 IGF-1 和 BMP-7 水平明显高于单独的 RPTECs。
我们的研究结果表明，与 RPTECs 共培养具有用于肾脏替代治疗的巨大潜力，从而为制造生物人工肾脏提供了基础信息。
