New Study Unveils Breakthrough Model for Human Kidney Development

Unprecedented window into early kidney development

Researchers have developed the first long-term, serum-free culture system for human fetal kidney organoids (hFKOs), offering an unprecedented window into early kidney development and disease.

The work, published in The EMBO Journal, was led by SCRM director Prof. Benjamin Dekel and colleagues at Sheba Medical Center, Tel Aviv University, and collaborating institutions.

Ynet spotlighted this groundbreaking research in a feature titled "ראשונים בעולם: חוקרים מישראל מגדלים רכיבי כליה אנושית במעבדה"

The team generated hFKOs from mid-gestation human fetal kidney tissue, which self-organized into complex, polarized structures resembling native kidney epithelium. Using advanced bulk and single-cell RNA sequencing, they mapped the organoids’ diverse cell populations — from nephron progenitors to mature tubules and podocytes — and demonstrated that these models faithfully preserve the developmental hierarchy seen in vivo.

Importantly, hFKOs showed high expression of Notch signaling genes, enabling the researchers to test the effects of Notch inhibition at single-cell resolution. Blocking Notch with the drug DAPT caused a maturation block in proximal tubules, enhanced distal tubule development, and revealed a previously undescribed prominin-1–expressing bipotent cell state capable of generating both proximal and distal fates.

This system overcomes key limitations of stem-cell–derived kidney organoids, which often fail to mature fully and lack consistent progenitor pools. By maintaining human kidney development in vitro for over six months, hFKOs open new avenues for studying congenital kidney diseases, such as Alagille syndrome, and for benchmarking regenerative medicine strategies.

"Our model captures developmental stages that no other in vitro system can," says Prof. Benjamin Dekel. "It’s a powerful platform for understanding human nephrogenesis and for testing therapeutic interventions."