NDLI: Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool.

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Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lombaert, Isabelle M. A. Brunsting, Jeanette F. Wierenga, Pieter K. Kampinga, Harm H. de Haan, Gerald Coppes, Robert P.
Description	Country affiliation: Netherlands Author Affiliation: Lombaert IM ( Department of Cell Biology, Section Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.)
Abstract	Irradiation of salivary glands during radiotherapy treatment of patients with head and neck cancer evokes persistent hyposalivation. This results from depletion of stem cells, which renders the gland incapable of replenishing saliva to produce acinar cells. The aim of this study was to investigate whether it is possible to expand the salivary gland stem/progenitor cell population, thereby preventing acinar cell depletion and subsequent gland dysfunction after irradiation. To induce cell proliferation, keratinocyte growth factor (DeltaN23-KGF, palifermin) was administered to C57BL/6 mice for 4 days before and/or after local irradiation of salivary glands. Salivary gland vitality was quantified by in vivo saliva flow rates, morphological measurements, and a newly developed in vitro salisphere progenitor/stem cell assay. Irradiation of salivary glands led to a pronounced reduction in the stem cells of the tissues, resulting in severe hyposalivation and a reduced number of acinar cells. DeltaN23-KGF treatment for 4 days before irradiation indeed induced salivary gland stem/progenitor cell proliferation, increasing the stem and progenitor cell pool. This did not change the relative radiation sensitivity of the stem/progenitor cells, but, as a consequence, an absolute higher number of stem/progenitor cells and acinar cells survived after radiation. Postirradiation treatment with DeltaN23-KGF also improved gland function, and this effect was much more pronounced in DeltaN23-KGF pretreated animals. Post-treatment with DeltaN23-KGF seemed to act through accelerated expansion of the pool of progenitor/stem cells that survived the irradiation treatment. Overall, our data indicate that DeltaN23-KGF is a promising drug to enhance the number of salivary gland progenitor/stem cells and consequently prevent radiation-induced hyposalivation. Disclosure of potential conflicts of interest is found at the end of this article.
File Format	HTM / HTML
ISSN	10665099
Issue Number	10
Volume Number	26
e-ISSN	15494918
Journal	STEM CELLS
Language	English
Publisher	Wiley
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Embryology Abnormalities, Radiation-induced Prevention & Control Fibroblast Growth Factor 7 Pharmacology Mutant Proteins Salivary Glands Cytology Radiation Effects Stem Cells Drug Effects Animals Cell Count Cell Proliferation Cell Survival Female Mice Mice, Inbred C57bl Radiation, Ionizing Physiopathology Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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