# Transplantation of Cryopreserved Thymus

> **NIH NIH R21** · DUKE UNIVERSITY · 2024 · $201,250

## Abstract

ABSTRACT: Transplantation of Cryopreserved Thymus
Advances in immunosuppression have improved patient outcomes after transplantation, but also place
patients at risk of life-threatening infection and end-organ failure. Development of immune tolerance to the
donor that eliminates the need for continuing immunosuppression would likely improve patient survival. Our
pivotal prior work showed that cultured thymus tissue implantation (CTTI) into athymic humans can
establish an immune system that is tolerant to antigens present on the donor thymus, while maintaining
tolerance to recipient native tissue. We have extended these findings to reprogram the immune system of
immunocompetent rats to recognize a transplanted donor heart as “self” using CTTI combined with
transplantation of heart from the same donor. In August 2021, our team performed the first human
CTTI/heart co-transplantation under eIND. The recipient is currently robustly producing naïve T cells within
the implanted donor thymus and testing for tolerance is pending. However, a major hurdle to translating this
approach more widely is that CTTI using freshly cultured thymus must occur between 12-21 days post-
thymus/heart harvest. Development of strategies to preserve the reconstitution potential of donor thymus
slices beyond 12-21 days would allow CTTI to be delayed until recipients are clinically stable and could
eventually extend the benefits of CTTI to all recipients via banked, donor-matched thymus. Our team has
developed methods for cryopreservation and thawing of cultured thymus tissue from both pigs and humans
that appear to maintain its viability, while continuing to meet CTTI quality criteria. This proposal aims to
determine the ability of cryopreserved cultured thymus tissue implantation (cCTTI) to re-establish thymus
function and naïve T cell numbers in thymectomized and conditioned recipient pigs. These studies will
leverage our unparalleled expertise as the only institution performing clinical CTTI in the Western
hemisphere to provide critical proof of concept for using cryopreserved thymus to induce immune tolerance
in the setting of human thymus-heart co-transplantation.

## Key facts

- **NIH application ID:** 10802406
- **Project number:** 5R21AI175164-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Laura P. Hale
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2023-03-06 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802406

## Citation

> US National Institutes of Health, RePORTER application 10802406, Transplantation of Cryopreserved Thymus (5R21AI175164-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10802406. Licensed CC0.

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