# Matricellular Signaling in Engineered Tracheal Transplantation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $391,476

## Abstract

ABSTRACT
Tracheal deficiency of any cause represents a potentially fatal process. Presently there are no
available substitutes for the trachea and it remains one of the few vital organs that can neither
be reconstructed from other tissues nor effectively transplanted. Researchers have begun to
explore the possibility of organ replacements from scaffolds (decellularized trachea) that can
then be transplanted to a patient. However, these first cases have been troubled by a range of
serious problems, including patient death, all ultimately linked to a lack of healing. We believe
that the lack of healing could be related to the secreted protein thrombospondin-1 (TSP1) an
identified anti-angiogenic agent that binds to matrix and to cell receptors and is induced by
healing tracheal cells. We found that limiting TSP1 signaling through agents that prevent its
binding to a specific cell membrane receptor, CD47, which is expressed on tracheal epithelial,
vascular and non-vascular cells, increases cell restoration of decellularized tracheal scaffolds
and tissue healing of transplanted decellularized tracheal scaffolds. We have developed several
technologies that target the maladaptive TSP1-CD47 signal including CD47-specific antibody,
peptide and morpholino. In tracheal cells we will test these technologies to increase cellular
restoration of decellularized 2- and 3-D tracheal scaffolds, the later with a unique bioreactor.
Bench top results will inform experiments to test these novel engineered tracheal transplants to
heal tracheal loss in rodent and canine models of orthotopic tracheal transplantation. As
humanized versions of CD47 targeting technologies are in development, and in the case of
CD47 antibodies in clinical trials, results from this proposal will support accelerated translation
into the clinic.

## Key facts

- **NIH application ID:** 9999659
- **Project number:** 5R01HL136494-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Stephen F. Badylak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,476
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999659

## Citation

> US National Institutes of Health, RePORTER application 9999659, Matricellular Signaling in Engineered Tracheal Transplantation (5R01HL136494-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999659. Licensed CC0.

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