# Engineering induction and assembly of human kidney tissue

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $425,765

## Abstract

PROJECT SUMMARY
The goal of this proposal is to study and control nephron induction and assembly towards the formation
of replacement renal tissue. Kidney organoids re-create an astonishing cellular diversity comparable to the
early fetal kidney. However, structural connectivity of urine-producing nephrons and their drainage network
formed by ureteric epithelium (UE) is required to avoid rapid pathology, yet has not been achieved. Accordingly,
there is an urgent need to achieve connectivity between nephrons and ureteric epithelium before kidney
organoids can achieve their potential in regenerative medicine. Our long-term goal is to construct ‘higher-order’
synthetic kidney tissues using human autologous stem cell lineages and assembly technologies that mimic the
outcomes of morphogenesis. Our overall objectives at this stage are firstly to gain spatial control over nephron
formation by determining how the mechanical microenvironment contributes to their induction sites and
maturation. Its second objective is to direct nephron fusion with UE at many spatial sites through a controlled
invasive process. Achieving these objectives will mark a transformative advance towards creating replacement
kidney tissue. Our central hypothesis is that mechanical compaction of mesenchymal cells during kidney
morphogenesis permits nephron induction, and subsequently that tight spatiotemporal control over WNT
signaling events is necessary for their efficient fusion with UE. We plan to achieve the objectives through two
specific aims. Firstly, we will determine the mechanical basis of nephrogenesis and use it to specify
nephron positions. We will study mechanical compaction of the nephrogenic mesenchyme, assess biophysical
properties of early nephron cells, and optimize nephrogenesis at specific locations using micropatterning
technology. Secondly, we will program WNT-induced fusion of nephrons with ureteric epithelium. We will
optimize fusion in nephron-ureteric epithelial co-cultures using optogenetic control over WNT signaling, and then
trigger nephron assembly with UE spheroids after transferring them from micropatterned surfaces. The proposed
research is innovative because we create fundamental knowledge while creating tissues that are biomaterial-
free, human-derived (compatible with patient-derived autologous cell strategies), and therefore open to future
development for transplantation. The proposed research is significant because higher-order assembly of human
kidney tissue will create a step-change in renal replacement technology beyond dialysis, transplant, and “abiotic”
filtration. We expect these efforts to have significant positive impact in the areas of fundamental biological
discovery, drug target screening, and regenerative medicine.

## Key facts

- **NIH application ID:** 10810649
- **Project number:** 5R01DK132296-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Alex Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $425,765
- **Award type:** 5
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10810649

## Citation

> US National Institutes of Health, RePORTER application 10810649, Engineering induction and assembly of human kidney tissue (5R01DK132296-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10810649. Licensed CC0.

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