Precision-cut human kidney slices as a model to elucidate the process of renal fibrosisStribos, E. G. D., Luangmonkong, T., Leliveld, A. M., de Jong, I. J., van Son, W. J., Hillebrands, J-L., Seelen, M. A., van Goor, H., Olinga, P. & Mutsaers, H. A. M., Apr-2016, In : Translational Research. 170, p. 8-16 9 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Pharmaceutical Technology and Biopharmacy
- Center for Medical Imaging (CMI)
- Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Groningen Kidney Center (GKC)
- Vascular Ageing Programme (VAP)
- Groningen Institute for Organ Transplantation (GIOT)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor beta 1 (TGF-beta 1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-beta 1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and alpha-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.
|Number of pages||9|
|Publication status||Published - Apr-2016|
- GROWTH-FACTOR-BETA, MESENCHYMAL TRANSITION, HUMAN PODOCYTES, DISEASE, LIVER, EXPRESSION, GLUCURONIDATION, FIBROBLASTS, FAILURE, TISSUES