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Abstract: SA-PO325

Generation of Human Kidney Organoids with Three-Dimensional Vascular-Like Systems

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 600 Development, Stem Cells, and Regenerative Medicine

Author

  • Peng, Kexin, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China
Background

Kidney organoids are hampered by their inability to imitate mature organ architecture since they are lack of vasculature, which creates essential niches. Here, we demonstrate two novel paradigms for generating three-dimensional vascularized kidney organoids.

Methods

Method 1. We differentiated the HiPSCs into kidney organoids and blood vessel organoids respectively. Then we co-cultured the 3D blood vessel networks with kidney progenitor aggregates to form the assembloids.

Method 2. We induced the HiPSCs into the kidney progenitor aggregates. Then we transfected with mCherry-hETV2 plasmids into kidney progenitor cells. 7 days later, the organoid got matured.

Results

Generation of assembloids from blood vessel networks and kidney progenitor aggregates
To study organ-to-organ communication circuits within different organoids, we co-cultured the blood vessel organoid and kidney organoid. At later stage, the blood vessel networks penetrated the entire kidney organoid and assembled into multiple lineage organoids, enabling us to study the characteristic of the micro-physiological system within different organoids.

hETV2 promotes the vascularization of kidney organoids
We transfected with mCherry-hETV2 plasmids into the kidney progenitor aggregates. The hETV2 overexpressing kidney organoid positioned podocytes (NPHS1+) and tubular parts (LTL+) packed with numerous endothelial networks (CD31+).

Conclusion

1) Blood vessel organoids penetrated the kidney progenitor aggregates, and formed entiely blood vessel networks within kidney organoids.
2) hETV2 transcription factor elicited the process of vascularization for kidney organoid.

A. Schematic diagram, B. Kidney organoid, C. Blood vessel organoid, D. CD31 and PDGFR-β

A. Assembloid, B. hETV2 expressing organoid

Funding

  • Government Support – Non-U.S.