Mobilization of bone marrow stem cells by granulocyte colony-stimulating factor ameliorates radiation-induced damage to salivary glands.
OBJECTIVE
One of the major reasons for failure of radiotherapeutic cancer treatment is the limitation in dose that can be applied to the tumor because of coirradiation of the normal healthy tissue. Late radiation-induced damage reduces the quality of life of the patient and may even be life threatening. Replacement of the radiation-sterilized stem cells with unirradiated autologous stem cells may restore the tissue function. Here, we assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived cells (BMC) to regenerate and functionally restore irradiated salivary glands used as a model for normal tissue damage.


METHODS
Male-eGFP+ bone marrow chimeric female C57BL/6 mice were treated with G-CSF, 10 to 60 days after local salivary gland irradiation. Four months after irradiation, salivary gland morphology and flow rate were assessed.


RESULTS
G-CSF treatment induced homing of large number of labeled BMCs to the submandibular glands after irradiation. These animals showed significant increased gland weight, number of acinar cells, and salivary flow rates. Donor cells expressed surface markers specific for hematopoietic or endothelial/mesenchymal cells. However, salivary gland acinar cells neither express the G-CSF receptor nor contained the GFP/Y chromosome donor cell label.


CONCLUSIONS
The results show that BMCs home to damaged salivary glands after mobilization and induce repair processes, which improve function and morphology. This process does not involve transdifferentiation of BMCs to salivary gland cells. Mobilization of BMCs could become a promising modality to ameliorate radiation-induced complications after radiotherapy.
Section of Radiation and Stress Cell Biology, Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Isabelle M A
IM
Lombaert
Pieter K
PK
Wierenga
Tineke
T
Kok
Harm H
HH
Kampinga
Gerald
G
deHaan
Robert P
RP
Coppes
D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D013997:Time Factors
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins