Rescue of salivary gland function after stem cell transplantation in irradiated glands.
Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome). In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit(+) cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.
Lombaert
Isabelle M A
IM
Section Radiation and Stress Cell Biology, Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Brunsting
Jeanette F
JF
Wierenga
Pieter K
PK
Faber
Hette
H
Stokman
Monique A
MA
Kok
Tineke
T
Visser
Willy H
WH
Kampinga
Harm H
HH
de Haan
Gerald
G
Coppes
Robert P
RP
D000818:Animals; D002454:Cell Differentiation / Q000528:radiation effects; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000528:radiation effects; D018987:Salivary Ducts / Q000166:cytology / Q000528:radiation effects; D012469:Salivary Glands / Q000166:cytology* / Q000528:radiation effects*; D018874:Spheroids, Cellular / Q000166:cytology / Q000528:radiation effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000528:radiation effects; D014965:X-Rays
D019009:Proto-Oncogene Proteins c-kit