# Identifying pathways required for integration of kidney organoid and host epithelia

> **NIH NIH UC2** · MOUNT DESERT ISLAND BIOLOGICAL LAB · 2020 · $627,808

## Abstract

Project Summary
Kidney disease is the 9th leading cause of death in the U.S. Because few therapies exist to prevent or slow
progression, over 700,000 patients have End Stage Renal Disease. These patients are treated with dialysis or
renal transplant, the latter resulting in markedly superior survival. However, kidney donors are limited and there
is an important unmet need for strategies that enhance renal repair or generate new nephrons for renal
replacement. Pluripotent stem cell derived organoids display key features of differentiated kidney tubules and
glomerular structures in vitro, and we have shown that they generate patterned nephrons in vivo displaying
kidney functions such as filtration and glucose uptake by the proximal tubule. To develop this technology for
renal replacement, stem cell derived tubules must be connected to host tubules for urinary output. Our recent
work in the zebrafish demonstrated that FGF signaling acts as a chemotactic signal to recruit and polarize cells
at sites of new nephron formation and canonical Wnt signaling is required for invasive cell rearrangement to
connect tubule lumens. Additional signaling pathways including non-canonical wnt signaling are also likely to
play a role in tubule interconnection. To fully explore the requirements for tubule interconnection we have
established a synergistic, three-part discovery platform comprising 1) genetic analysis of in vivo new nephron
addition in the regenerating zebrafish adult kidney, 2) in vitro 3D cell culture analysis of mammalian epithelial
fusion, and 3) in vivo stem cell-derived kidney organoid engraftment to a host mouse collecting system. We will
combine these approaches to analyze multiple steps of the tubule fusion process involving 1) recruitment of
nephron progenitor cells to target epithelia, 2) removal of intervening ECM/basement membranes, 3) patterned
collective cell invasion of target epithelia, and 4) establishment of a continuous patent new lumen to convey the
nephron filtrate. These studies will provide important new insights about an essential but understudied cellular
mechanism that will be required for in vivo engraftment of new kidney tissue-based renal regeneration
therapies.

## Key facts

- **NIH application ID:** 10053465
- **Project number:** 1UC2DK126021-01
- **Recipient organization:** MOUNT DESERT ISLAND BIOLOGICAL LAB
- **Principal Investigator:** IAIN A. DRUMMOND
- **Activity code:** UC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,808
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053465

## Citation

> US National Institutes of Health, RePORTER application 10053465, Identifying pathways required for integration of kidney organoid and host epithelia (1UC2DK126021-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053465. Licensed CC0.

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