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

Rose V, Fink D, Krüger R, Kraus A, Schödel J, Schiffer M, Müller-Deile J (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 15

Article Number: 37730

Journal Issue: 1

DOI: 10.1038/s41598-025-25650-9

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.

Authors with CRIS profile

Victoria Rose Department of Medicine 4 – Nephrology and Hypertension René Krüger Department of Medicine 4 – Nephrology and Hypertension Johannes Schödel Department of Medicine 4 – Nephrology and Hypertension Mario Schiffer Lehrstuhl für Innere Medizin IV Janina Müller-Deile Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Innovations-Institut für Nanotechnologie und korrelative Mikroskopie e.V. (INAM) / Institute for Nanotechnology and Correlative Microscopy DE Germany (DE)

How to cite

APA:

Rose, V., Fink, D., Krüger, R., Kraus, A., Schödel, J., Schiffer, M., & Müller-Deile, J. (2025). Patient-specific hiPSC-Podocytes as an in vitro model of genetic FSGS. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-25650-9

MLA:

Rose, Victoria, et al. "Patient-specific hiPSC-Podocytes as an in vitro model of genetic FSGS." Scientific Reports 15.1 (2025).

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