期刊
DEVELOPMENTAL BIOLOGY
卷 477, 期 -, 页码 98-116出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2021.04.009
关键词
Endothelial cell; Angioblast; Blood vessel; Cord; Kidney; RNAseq; Organoid
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [DK106743, DK079862]
- National Institute of Heart, Lung and Blood [HL113498]
- Center for Regenerative Science and Medicine (CRSM) predoctoral fellowship
- American Society of Nephrology PreDoctoral Fellowship Award
- [F31 DK124046]
Kidney organoids offer a promising model system to study vascular-nephron interactions, but face unique challenges in establishing and maintaining a vascular network when grown ex vivo.
Chronic kidney disease (CKD) and end stage renal disease (ESRD) are increasingly frequent and devastating conditions that have driven a surge in the need for kidney transplantation. A stark shortage of organs has fueled interest in generating viable replacement tissues ex vivo for transplantation. One promising approach has been self-organizing organoids, which mimic developmental processes and yield multicellular, organ-specific tissues. However, a recognized roadblock to this approach is that many organoid cell types fail to acquire full maturity and function. Here, we comprehensively assess the vasculature in two distinct kidney organoid models as well as in explanted embryonic kidneys. Using a variety of methods, we show that while organoids can develop a wide range of kidney cell types, as previously shown, endothelial cells (ECs) initially arise but then rapidly regress over time in culture. Vasculature of cultured embryonic kidneys exhibit similar regression. By contrast, engraftment of kidney organoids under the kidney capsule results in the formation of a stable, perfused vasculature that integrates into the organoid. This work demonstrates that kidney organoids offer a promising model system to define the complexities of vascular-nephron interactions, but the establishment and maintenance of a vascular network present unique challenges when grown ex vivo.
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