# Canine Disease and Transplantation Model

> **NIH NIH U54** · FRED HUTCHINSON CANCER CENTER · 2024 · $51,114

## Abstract

PROJECT SUMMARY/ABSTRACT - Canine Disease and Transplantation Model (Canine) Core
Hematopoiesis is a complex process which is regulated by many internal and external factors. Numerous
variables synergize or antagonize to influence differentiation and stem cell maintenance. These mechanisms
that control the hematopoietic system are difficult to deconstruct into fundamental parts. Thus, hematopoietic
stem cells are difficult to maintain in vitro, because the cells' responses to culture conditions are dictated by so
many influences. The conclusions drawn from in vitro cell-based assays are then necessarily limited by the
complexity of the system. There are many meritorious reasons to manipulate stem cells: correct a mutation,
render them drug resistance, and control their antigenic profile to name a few. They can be modified for
several purposes, but critically they must retain stem cell function. The only definitive assay for stem cell
function is hematopoietic reconstitution following lethal conditioning. Therefore, animal model systems are
used to reveal the fundamental biology of hematopoietic stem cells. However, no single animal model can fully
recapitulate the human hematopoietic system, so we propose to offer the canine as a model to complement
hematopoietic studies in mice. Canines address some of the key differences between mice and humans
notably size, lifespan, and genetic diversity. Additionally, dogs have relatively large litters, which can be useful
for histocompatibility and transplantation. This Canine Core will use engineered somatic mutations,
spontaneous germline mutations, and develop canine biological reagents for non-malignant hematopoietic
research. The accumulated knowledge of canine husbandry and stem cell transplantation, as well as existing
facilities at Fred Hutch, make this Canine Core unique. In conjunction with the expertise of the other CCEH
Cores, the entire breadth of an experiment can be completed. The Cell P&P core can isolate and store stem
cells, these cells can be modified in the Tools core, the stem cell character can be verified in a canine-to-
mouse transplant in the Xenografting Core, and the Canine Core can provide a large animal in vivo model to
study the biology of stem cell modifications. Internal and external users of this core will be able to take
advantage of decades of experience enriching stem cells, manipulating them, and assaying them in
xenografts, as well as the 60 years of institutional experience with the canine model.

## Key facts

- **NIH application ID:** 10899766
- **Project number:** 5U54DK106829-10
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Brian Joseph Hayes
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $51,114
- **Award type:** 5
- **Project period:** 2015-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899766

## Citation

> US National Institutes of Health, RePORTER application 10899766, Canine Disease and Transplantation Model (5U54DK106829-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10899766. Licensed CC0.

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