# Cell-Based Therapy in Minipig Model of Radiation-Induced Xerostomia

> **NIH NIH R56** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $404,519

## Abstract

This project will develop a fully functional, implantable human salivary gland for patients suffering from
xerostomia/dry mouth after radiotherapy for head and neck cancer. Despite the regulatory requirement for a
close-to-human animal model for clinical translation of tissue engineered organs, large animal models do not
exist to test stem-cell approaches to restore salivary function including fluid secretion and protein production
needed for digestion and oral health. Rodent models, while useful to test product designs, lack key attributes
needed to deliver an implantable biological device to the clinic. To address these shortcomings, we assembled
an interdisciplinary team that includes the Farach-Carson/Harrington team in Houston, the Passineau laboratory
in Pittsburgh to develop an approach using a radiated pig model amenable to genetic manipulation, and the
Lombaert laboratory in Ann Arbor to assess implant integration. Our recent demonstration that a human-in-pig
model under immunosuppression is well tolerated presents an unprecedented opportunity to develop xenograft
model for the salivary human stem/progenitor cell (hS/PC) transplantation studies and avoid the need to develop
a pig-in-pig autograft. This proposal builds on our exciting preliminary results to develop and characterize a novel
radiated immunosuppressed mini-pig model for testing the ability of transplanted hS/PCs to restore salivary
secretory function. We hypothesize that this model will recapitulate the environment of the radiated human
salivary bed, and provide the type of information needed to evaluate the function of human S/P cells one day to
be transplanted into patients suffering from xerostomia. Specific Aims are: 1) Establish the radiated
immunosuppressed minipig as a suitable host animal to evaluate the long term stability, biocompatibility and fate
of matrix-modified hyaluronate (HA) hydrogel materials containing encapsulated hS/PCs; a) Develop and
standardize optimized strategies to place the salivary neotissue prototype in the host parotid bed; b) Evaluate
stability of implanted acellular hydrogel constructs at various times after placement in the radiated parotid and
make formulational changes as needed to ensure long term biointegration; c) Use a quantitative scoring system
to evaluate the fate over time of encapsulated hS/PC-loaded constructs after transplantation into the radiated
salivary bed including viability, growth without overgrowth, host integration including vasculature and nerve, and
differentiation into salivary structures expressing acinar, ductal and myoepithelial markers. 2) Evaluate the ability
of the transplanted tissue to restore salivary function: a) Demonstrate functional protein delivery from the
salivary neotissues into the irradiated minipig by combining restorative gene therapy with implanted salivary
neotissues; b) Demonstrate restoration of fluid flow by evaluating aquaporin 5 expression in neotissues and fluid
production using direct...

## Key facts

- **NIH application ID:** 10214978
- **Project number:** 1R56DE026530-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** MARY C FARACH-CARSON
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $404,519
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214978

## Citation

> US National Institutes of Health, RePORTER application 10214978, Cell-Based Therapy in Minipig Model of Radiation-Induced Xerostomia (1R56DE026530-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10214978. Licensed CC0.

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