TY - JOUR
T1 - Characterization of Transgenic NSG-SGM3 Mouse Model of Precision Radiation-Induced Chronic Hyposalivation
AU - Musheer Aalam, Syed Mohammed
AU - Viringipurampeer, Ishaq A.
AU - Walb, Matthew C.
AU - Tryggestad, Erik J.
AU - Emperumal, Chitra P.
AU - Song, Jianning
AU - Xu, Xuewen
AU - Saini, Rajan
AU - Lombaert, Isabelle M.A.
AU - Sarkaria, Jann N.
AU - Garcia, Joaquin
AU - Janus, Jeffrey R.
AU - Kannan, Nagarajan
N1 - Publisher Copyright:
© 2022 by Radiation Research Society. All rights of reproduction in any form reserved.
PY - 2022/7/12
Y1 - 2022/7/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85138126021&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138126021&partnerID=8YFLogxK
U2 - 10.1667/RADE-21-00237.1
DO - 10.1667/RADE-21-00237.1
M3 - Article
C2 - 35820185
AN - SCOPUS:85138126021
SN - 0033-7587
VL - 198
SP - 243
EP - 254
JO - Radiation Research
JF - Radiation Research
IS - 3
ER -