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<p>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 (<i>INF2</i>) 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月28日

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  • Victoria Rose,
  • Denise Fink,
  • René Krüger,
  • Annalena Kraus,
  • Johannes Schödel,
  • Mario Schiffer,
  • Janina Müller-Deile

摘要

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.