Human kidney organoids produce functional renin.

Human kidney organoids produce functional renin.:

Human kidney organoids produce functional renin.

Kidney Int. 2020 Sep 09;:

Authors: Shankar AS, Du Z, Mora HT, van den Bosch TPP, Korevaar SS, Van den Berg-Garrelds IM, Bindels E, Lopez-Iglesias C, Groningen MC, Gribnau J, Baan CC, Danser AHJ, Hoorn EJ, Hoogduijn MJ

Abstract

Renin production by the kidney is of vital importance for salt, volume, and blood pressure homeostasis. The lack of human models hampers investigation into the regulation of renin and its relevance for kidney physiology. To develop such a model, we used human induced pluripotent stem cell derived kidney organoids to study the role of renin and the renin-angiotensin system in the kidney. Extensive characterization of the kidney organoids revealed kidney-specific cell populations consisting of podocytes, proximal and distal tubular cells, stromal cells and endothelial cells. We examined the presence of various components of the renin-angiotensin system such as angiotensin II receptors, angiotensinogen and angiotensin converting enzyme 1 and 2. We identified by single cell sequencing, immunohistochemistry and functional assays that cyclic AMP stimulation induces a subset of pericytes to increase the synthesis and secretion of enzymatically active renin. Renin production by the organoids was responsive to regulation by parathyroid hormone. Subcutaneously implanted kidney organoids in immunodeficient IL2Ry-/-RAG2-/- mice were successfully vascularized, maintained tubular and glomerular structures and retained capacity to produce renin two months after implantation. Thus, our results demonstrate that kidney organoids express renin and provide insights into the endocrine potential of human kidney organoids, which is important for regenerative medicine in the context of the endocrine system.



PMID: 32918942 [PubMed - as supplied by publisher]