# Recapitulation of the salivary gland niche ex vivo for stem cell-based therpies

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $377,360

## Abstract

Project Summary
Saliva is an important defense mechanism for protecting oral health. Salivary gland (SG) hypofunction
results in uncontrolled and severe oral diseases that lead to severely compromised quality of life. SGs
are highly differentiated and have little regenerative capacity once they are destroyed by therapy or
disease (e.g. radiation therapy or autoimmune Sjögren’s syndrome). Therefore, the development of
strategies for preserving or regenerating the secretory function of SGs is essential for successful
management of these patients. The extracellular matrix (ECM) is a major component of the unique
microenvironment or “niche” that directs and maintains the differentiated functions of cells in vivo
Presently, there are two main obstacles to stem cell-based regenerative therapies: 1) the limited
availability of multi-potent stem cells and 2) the difficulty of selectively controlling the differentiation
multi-potent stem cells into the desired cell lineage. Our research group has developed a novel ECM-
based cell culture system for expanding multipotent mesenchymal stem cells (MSCs) from bone
marrow and 3D silk fibroin scaffolds (SFS) for establishing the SG niche ex vivo. Therefore, we
propose to test the hypothesis that salivary gland specific ECM (SG-ECM), established on a natural 3D
SFS, is a biomimetic niche capable of directing MSC proliferation and differentiation into functional SG
progenitor cells. In Specific Aim 1, we will optimize scaffold characteristics for the production of SG-
ECM on the SFS by primary SG epithelial cells. In Specific Aim 2, we will determine whether the
optimal SG-ECM coated SFS directs MSC differentiation into the SG cell lineage. In Specific Aim 3, the
efficacy of the cells, produced in Specific Aim 2, will be evaluated in an in vivo model of SG damage
due to irradiation.
The novelty of this proposal includes (1) testing our novel cell culture technology to obtain sufficient
numbers of multipotent MSCs from human bone marrow to repair or regenerate SG function; (2) testing
a natural 3D scaffold material and optimizing its properties for supporting SG regeneration and tissue
engineering; (3) examining the role of SG-derived ECM coated scaffolds in directing MSC differentiation
to the SG cell lineage and functional SG units, and (4) assembling a multidisciplinary team to study
stem-cell based SG therapy. The success of this study may lead to new therapeutic strategies for
clinical management of SG dysfunction.

## Key facts

- **NIH application ID:** 9973250
- **Project number:** 5R01DE025286-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** XIAO-DONG CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,360
- **Award type:** 5
- **Project period:** 2016-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973250

## Citation

> US National Institutes of Health, RePORTER application 9973250, Recapitulation of the salivary gland niche ex vivo for stem cell-based therpies (5R01DE025286-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973250. Licensed CC0.

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