Characterization of Transgenic NSG-SGM3 Mouse Model of Precision Radiation-Induced Chronic Hyposalivation.

Autor:	Musheer Aalam SM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Viringipurampeer IA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Walb MC; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Tryggestad EJ; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Emperumal CP; Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota., Song J; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Xu X; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Saini R; Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada., Lombaert IMA; Biointerfaces Institute, School of Dentistry, Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Michigan., Sarkaria JN; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Garcia J; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Janus JR; Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota.; Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Jacksonville, Florida.; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota., Kannan N; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota.; Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota.
Jazyk:	angličtina
Zdroj:	Radiation research [Radiat Res] 2022 Sep 01; Vol. 198 (3), pp. 243-254.
DOI:	10.1667/RADE-21-00237.1
Abstrakt:	Regenerative medicine holds promise to cure radiation-induced salivary hypofunction, a chronic side effect in patients with head and neck cancers, therefore reliable preclinical models for salivary regenerative outcome will promote progress towards therapies. In this study, our objective was to develop a cone beam computed tomography-guided precision ionizing radiation-induced preclinical model of chronic hyposalivation using immunodeficient NSGSGM3 mice. Using a Schirmer's test based sialagogue-stimulated saliva flow kinetic measurement method, we demonstrated significant differences in hyposalivation specific to age, sex, precision-radiation dose over a chronic (6 months) timeline. NSG-SMG3 mice tolerated doses from 2.5 Gy up to 7.5 Gy. Interestingly, 5-7.5 Gy had similar effects on stimulated-saliva flow (∼50% reduction in young female at 6 months after precision irradiation over sham-treated controls), however, >5 Gy led to chronic alopecia. Different groups demonstrated characteristic saliva fluctuations early on, but after 5 months all groups nearly stabilized stimulated-saliva flow with low-inter-mouse variation within each group. Further characterization revealed precision-radiation-induced glandular shrinkage, hypocellularization, gland-specific loss of functional acinar and glandular cells in all major salivary glands replicating features of human salivary hypofunction. This model will aid investigation of human cell-based salivary regenerative therapies. (©2022 by Radiation Research Society. All rights of reproduction in any form reserved.)
Databáze:	MEDLINE
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