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Kidney Week

Abstract: TH-PO0563

Amniotic Fluid Organoids Model the Developing Kidneys and Lungs

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Authors

  • Beckerman, Pazit, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Babosova, Olga, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Rabinowitz, Grace, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Jubany, Tammir, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Avnet, Hagai, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Barshack, Iris, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Dotan, Zohar A., Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Omer, Dorit, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Dekel, Benjamin, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Weisz, Boaz, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Levin-Klein, Rena, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel
  • Pleniceanu, Oren, Sheba Medical Center, Tel HaShomer, Tel Aviv District, Israel

Group or Team Name

  • Kidney Research Lab, Sheba Medical Center.
Background

Despite biomedical advances, major gaps regarding human development remain, and many developmental disorders lack treatment, representing a huge clinical burden. This results from fetuses being largely inaccessible for analysis.

Methods

We report robust protocols for generating kidney and lung organoids (AFKO and AFLO, respectively) from fetal cells in amniotic fluid (AF), which recapitulate fetal organs at the single-cell level.

Results

AFKO harbor key fetal kidney cell populations, including nephrogenic, urothelial and stromal, and can uptake albumin. Upon injection into the cortex of human fetal kidney explants, AFKO cells integrate into the progenitor niche and contribute to developing tubules. AFLO comprise alveolar cells and most airway cell types in a pseudostratified epithelial structure, upregulate surfactant expression upon steroid treatment, and show functional cystic fibrosis transmembrane conductance regulator (CFTR) channels.

Conclusion

This platform represents a new tool for modeling of developing organs, which relies on clinically available AF samples, and can thus be applied to virtually any fetus in real-time. Thus, it provides an accessible means to study developmental processes and mechanisms of developmental problems, such as congenital anomalies and prematurity-related problems, using bona fide human fetal cells, which until now has been challenging.

A. Scheme. B&C. AFKO Morphology and expression of kidney specific genes. D. RNA-seq of AFKO, showing expression of kidney-specific genes. E&F. AFKO harbor NPCs. G&H. Nephrogenic AFKO. I. RNA-seq, segment-specific markers. J. UB lineage AFKO. K. RNA-seq, stromal markers. L. RNA-seq, UB-lineage markers. M. AFKO possess cilia and proliferate, and stromal AFKO.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)