Safety evaluation of conditionally immortalized cells for renal replacement therapy.

Safety evaluation of conditionally immortalized cells for renal replacement therapy. Oncotarget. 2019 Sep 03;10(51):5332-5348 Authors: Mihajlovic M, Hariri S, Westphal KCG, Janssen MJ, Oost MJ, Bongiovanni L, van den Heuvel LP, de Bruin A, Hilbrands LB, Masereeuw R Abstract End-stage kidney disease represents irreversible kidney failure. Dialysis and transplantation, two main treatment options currently available, present various drawbacks and complications. Innovative cell-based therapies, such as a bioartificial kidney, have not reached the clinic yet, mostly due to safety and/or functional issues. Here, we assessed the safety of conditionally immortalized proximal tubule epithelial cells (ciPTECs) for bioartificial kidney application, by using in vitro assays and athymic nude rats. We demonstrate that these cells do not possess key properties of oncogenically transformed cells, including anchorage-independent growth, lack of contact inhibition and apoptosis-resistance. In late-passage cells we did observe complex chromosomal abnormalities favoring near-tetraploidy, indicating chromosomal instability. However, time-lapse imaging of ciPTEC-OAT1, confined to a 3D extracellular matrix (ECM)-based environment, revealed that the cells were largely non-invasive. Furthermore, we determined the viral integration sites of SV40 Large T antigen (SV40T), human telomerase (hTERT) and OAT1 (SLC22A6), the transgenes used for immortalization and c...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research