Abstract

There is a need to understand how organ regeneration can be established using stem cell- based therapy. Our goal is to develop clinical approaches for stem cell therapy to regenerate irradiated submandibular glands (SMGs). This is essential to restoring the oral and dental health of head-and-neck cancer patients who suffer from hypofunction after radiotherapy treatment. Our objective is to characterize and expand salivary gland stem cells, and identify conditions to optimize their regenerative capacity in an irradiated environment. The central hypothesis is that a subpopulation of Kit+ cells are stem cells that can be expanded in vitro and then stimulated in vivo after transplantation to regenerate an irradiated SMG. Thus, the following aims will be pursued: 1) characterization of the stem cells in the heterogeneous Kit+ population; 2) in vitro expansion of Kit+ stem cells; and 3) preservation of the stem cell environment in an irradiated gland. This will mainly be achieved by using transgenic mouse strains, cell sorting and transplantation, ChiP-seq and RNA sequencing analysis. The project is innovative because it addresses these aims by using stem cells from both human and mouse SMGs. Altogether, the proposal is expected to significantly progress clinical stem cell-based treatments for long-term SMG regeneration.

Public Health Relevance

This research is relevant to human health because stem cell-based therapy can restore hyposalivation, and it is relevant to the NIDCR's mission to re-establish oral and dental health in irradiated head-and-neck cancer patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Transition Award (R00)
Project #
5R00DE022557-04
Application #
9313882
Study Section
Special Emphasis Panel (NSS)
Program Officer
Chander, Preethi
Project Start
2015-08-05
Project End
2018-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Kirsch, David G; Diehn, Max; Kesarwala, Aparna H et al. (2018) The Future of Radiobiology. J Natl Cancer Inst 110:329-340
Lombaert, Isabelle; Movahednia, Mohammad M; Adine, Christabella et al. (2017) Concise Review: Salivary Gland Regeneration: Therapeutic Approaches from Stem Cells to Tissue Organoids. Stem Cells 35:97-105
Knox, Sarah M; Lombaert, Isabelle M A; Haddox, Candace L et al. (2013) Parasympathetic stimulation improves epithelial organ regeneration. Nat Commun 4:1494