Biology subjects

Klawitter, M.

Publications and source records attributed to Klawitter, M..

2 recordsLinked to original sources

bioRxiv2023

Nifurpirinol: A potent inducer of FSGS-like glomerular injury in transgenic zebrafish

Identifying effective drugs for focal segmental glomerulosclerosis (FSGS) treatment holds significant importance. Our high-content drug screening on zebrafish larvae relies on nitroreductase/metronidazole (NTR/MTZ)-induced podocyte ablation to generate FSGS-like injury. A crucial factor for successful drug screenings is minimizing variability in injury induction. For this, we introduce Nifurpirinol (NFP) as a more reliable prodrug for targeted podocyte depletion. NFP showed a 2.3-fold increase in efficiency at concentrations 1600-fold lower compared to MTZ-mediated injury induction. Integration into the screening workflow validated its suitability for the high-content drug screening. The presence of crucial FSGS hallmarks, including podocyte foot process effacement, proteinuria, and activation of parietal epithelial cells, was observed. In this study, we demonstrate that NFP serves as remarkably effective prodrug for inducing an FSGS-like phenotype in zebrafish larvae and proves to be well-suited for a high-content drug screening, aiding in the identification of potential candidates for FSGS treatment.

cell biology↗

bioRxiv2023

Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system

Neural stem cells (NSC) are considered to be valuable candidates for delivering a variety of anti-cancer agents to brain tumors, including oncolytic viruses. However, owing to the previously reported tumorigenic potential of NSC cell line after intranasal administration (INA), here we identified the human hepatic stellate cell line (LX-2) as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAV) as therapeutic cargo, and being non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX-2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic HSV-TK integration into LX-2 leading to the high vulnerability to Ganciclovir. Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno-compromised mice 3 months after INA of LX-2 cells. Our data suggest that LX-2 is a novel robust and safe cell line for delivering anti-cancer and other therapeutic agents to the brain.

molecular biology↗