# Genome engineering of stem cells for kidney regeneration.

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Acute kidney injury is a diagnosis associated with significant morbidity and mortality in the
Veteran population. Therefore, we propose to develop a regenerative treatment for acute kidney
injury based on progenitor cell exosomes. Recent studies suggest that the therapeutic effects of
stem or progenitor cells are at least partially mediated through exosomes, a subset of
extracellular vesicle. Exosomes are advantageous as they can be lyophilized for storage, are
generally non-immunogenic, and do not require culture of cells just prior to therapeutic
administration. The stem or progenitor cell type that will be utilized for this study is the induced
nephron progenitor cell. Nephron progenitor cells form most of the differentiated cell types of the
adult nephron, but are exhausted just prior to birth in humans. Induced nephron progenitors are
derived from adult human cells in tissue culture through transcription factor reprogramming with
inducible piggyBac transposons. The reprogramming factors are SNAI2, EYA1, and SIX1. We
have isolated and characterized exosomes from induced nephron progenitor cells and find them
to be abundant. Our preliminary data demonstrate that induced nephron progenitor exosomes
have regenerative and protective properties in the HK-2 tubule cell line, human kidney
organoids, and mouse models of acute kidney injury. However, further development is
necessary to bring this potential therapeutic forward from bench to bedside. In Aim 1, we
hypothesize that the exosomes will reduce markers of kidney injury in ischemia reperfusion and
rhabdomyolysis mouse models of acute kidney injury. We will administer the induced nephron
progenitor exosomes before, concurrent with, immediately after, and one day following injury
and evaluate histology as well as markers of kidney function to determine the therapeutic effects
on acute kidney injury. In Aim 2, we hypothesize that the induced nephron progenitor cell-
derived exosomes protect human tubule cells from apoptosis induced by nephrotoxicants
through specific protein and/or RNA species that can be modulated through genome
engineering strategies to further enhance nephron progenitor extracellular vesicle efficacy.
These studies will accelerate the translation of next-generation extracellular vesicle therapies
based on advanced cell and genome engineering techniques for treatment of acute kidney
injury.

## Key facts

- **NIH application ID:** 10803492
- **Project number:** 2I01BX004845-05
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Lauren Elizabeth Woodard
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2020-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803492

## Citation

> US National Institutes of Health, RePORTER application 10803492, Genome engineering of stem cells for kidney regeneration. (2I01BX004845-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10803492. Licensed CC0.

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