Kidney Week

Abstract: TH-PO400

Amniotic Fluid Organoids as Personalized Real-Time Models of the Fetal Kidney and Lung

Session Information

• Development, Organoids, Injury, and Regeneration
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Pleniceanu, Oren, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Oren Pleniceanu, MD, PhD

• Babosova, Olga, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Olga Babosova, PhD

• Weisz, Boaz, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Boaz Weisz, MD

• Rabinowitz, Grace, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Grace Rabinowitz

• Jubany, Tammir, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Tammir Jubany, MSc

• Avnet, Hagai, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Hagai Avnet, MD

• Pardo, Noam, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Noam Pardo, MD

• Barshack, Iris, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Iris Barshack, DrMed

• Omer, Dorit, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Dorit Omer

• Dotan, Zohar A., Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Zohar A. Dotan, MD, PhD

• Dekel, Benjamin, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Benjamin Dekel, MD, PhD

• Levin-Klein, Rena, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Rena Levin-Klein, PhD

• Beckerman, Pazit, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel

Pazit Beckerman, MD

Group or Team Name

• Kidney Research Lab, Sheba Medical Center.

Background

As fetuses are largely inaccessible, human development remains poorly understood, and many developmental disorders, such as kidney anomalies, lack therapy. We aimed to use amniotic fluid (AF), which comprises fetal urine and lung secretions, to model fetal kidneys and lungs.

Methods

AF was seeded in 'kidney' or 'lung' media, which select for the respective progenitors, generating 3D organoids mirroring both organs. These were analyzed by immunostainings, single cell RNA-seq and functional tests.

Results

We established single cell-derived AF kidney (AFKO) and lung organoids (AFLO). AFKO harbor nephrogenic, urothelial and stromal cells, and uptake albumin. Upon injection to human fetal kidney explants, AFKO cells populate the progenitor niche and contribute to nascent tubules. AFLO habor alveolar and airway cells, upregulate surfactant levels upon steroid treatment and show active CFTR channels.

Conclusion

We present a new tool for personalized modeling of fetal organs, applicable to virtually any fetus. This provides accessible means to study normal and abnormal development via bona fide human fetal cells, which until now has been difficult.

A-B. AFKO express renal markers. C. Renal gene expression; D. AFKO harbor SIX1⁺EpCAM^- & PAX2⁺EpCAM^- nephron progenitors (NP), generating SIX1^-EpCAM⁺ & PAX2^-EpCAM⁺ epithelia. E. NP marker expression. F. AFKO harbor tubules of multiple nephron segments. G. Segment-specific marker expression. H. SIX1⁺/PAX2⁺ NP give rise to EpCAM⁺ epithelia. I. UB lineage differentiation in AFKO: RET⁺ tip cells alongside AQP2⁺ collecting duct cells and UPK2⁺ urothelia. J. UB marker expression. K. AFKO have cilia and proliferate. L. MEIS1⁺ stromal AFKO. M. Stromal marker expression.

Funding

• Private Foundation Support