# Patient-specific hiPSC-Podocytes as an in vitro model of genetic FSGS

## TL;DR

The study uses patient-specific stem cell-derived podocytes to model genetic FSGS and test personalized treatments.

## Contribution

The novelty lies in using hiPSC-podocytes from an INF2-mutated patient to study FSGS and test drug responses in vitro.

## Key findings

- Patient-specific hiPSC-podocytes showed decreased protrusion length and disrupted actin filaments.
- Steroid treatment partially improved actin cytoskeleton in patient-derived cells.
- INF2 mutation is linked to altered podocyte function and response to treatment.

## Abstract

Mutations in podocyte-specific genes are associated with genetic focal segmental glomerulosclerosis (FSGS), yet the potential for targeted treatments remains uncertain. Therefore, patient-specific models are essential for understanding cellular phenotypes, identifying personalized therapies, and avoiding ineffective treatments. This study utilized patient-specific human induced pluripotent stem cell (hiPSC)-Podocytes to investigate cellular phenotypic and functional alterations associated with genetic FSGS in vitro. HiPSC-Podocytes were generated from a patient with a mutation in the inverted formin 2 (INF2) gene, who showed a partial clinical response to steroid treatment. Compared to healthy donor-derived hiPSC-Podocytes, the patient-specific hiPSC-Podocytes exhibited decreased protrusion length, reduced levels of actin-associated markers, and alterations in INF2 protein levels. Additionally, actin filaments were disrupted, characterized by increased actin depolymerization. Next to the actin-modulating agent Bis-T-23, the steroid Solu-Decortin H (SDH) improved the actin cytoskeleton in the patient-specific cells, which aligned with the patient’s partial response to steroids. This underscores the importance of personalized treatment strategies based on specific cellular responses in genetic FSGS.

The online version contains supplementary material available at 10.1038/s41598-025-25650-9.