# Developing approaches for universal organ transplantation

> **NIH NIH DP5** · STANFORD UNIVERSITY · 2021 · $400,392

## Abstract

Project Abstract/Summary (30 lines)
This proposal will explore the feasibility of universal organ transplantation. This new
stem cell-based approach may expand the versatility and safety of organ transplants.
The eventual goal is to transplant immunologically-foreign organs into patients without
recourse to long-term immune suppression. This goal will be realized by using stem-cell
differentiation and immune-system replacement to reset the immune barriers that usually
reject foreign organs. If successful, this might one day greatly expand the number of
patients that receive life-saving organ transplants. The research proposed herein will
also yield basic insight into developmental biology, stem cell biology and immunology.
 Organ transplants are life-saving therapies for patients with degenerative diseases
or organ failure. Degenerative diseases cause ~50% of adult deaths in developed
nations, and range from Parkinson's Disease to liver failure. However, the use of organ
transplants to treat degenerative diseases is often impeded by the immune system,
because the immune system rejects foreign tissues. Consequently, patients in need of
organ transplants must wait long periods on “the transplant list” pending the availability
of scarce immune-matched organs and/or must undergo dangerous long-term immune
suppression to accept mismatched organs—neither outcome is acceptable.
 The objective of universal organ transplantation is to transplant all human patients
with tissues artificially generated from a single human embryonic stem cell (hESC) line,
by overriding immune barriers that normally render this impractical. The approach is to
“reset” a patient's immune system by partially replacing it with a hESC-derived immune
system and then to transplant hESC-derived tissues. In such patients, their hESC-
derived immune system should permanently tolerate the transplanted hESC-derived
tissue, obviating the need for lifelong immune suppression to accept the new tissue. This
might one day enable many patients to receive lifesaving hESC-derived organs.
 To achieve this long-term goal, three capabilities must be developed: safe
depletion of pre-existing human immune systems (Aim #1), generation of new human
blood stem cells from ESCs (Aim #2) and generation of new human regulatory T cells
from ESCs (Aim #3). As such these projects will form the three parallel lines of
investigation of the current proposal to test the feasibility of universal organ
transplantation, starting from basic research and assays in humanized mouse models.

## Key facts

- **NIH application ID:** 10247750
- **Project number:** 5DP5OD024558-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** KYLE M LOH
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,392
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247750

## Citation

> US National Institutes of Health, RePORTER application 10247750, Developing approaches for universal organ transplantation (5DP5OD024558-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247750. Licensed CC0.

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