Regeneration of irradiated salivary glands with stem cell marker expressing cells

TY - JOUR

T1 - Regeneration of irradiated salivary glands with stem cell marker expressing cells

AU - Nanduri, Lalitha S Y

AU - Maimets, Martti

AU - Pringle, Sarah A

AU - van der Zwaag, Marianne

AU - van Os, Ronald P

AU - Coppes, Robert P

N1 - Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PY - 2011/6

Y1 - 2011/6

N2 - BACKGROUND: Stem cell therapy could be a potential way for reducing radiation-induced hyposalivation and improving the patient's quality of life. However, the identification and purification of salivary gland stem cells have not been accomplished. This study aims to better characterize the stem/progenitor cell population with regenerative potential residing in the mouse salivary gland.METHODS: Mouse submandibular gland tissue, isolated cells and cultured 3 day old salispheres were tested for their expression of stem cell markers c-Kit, CD133, CD49f, and CD24 using immunohistochemistry for tissue and flow cytometry for cells. Mice were locally irradiated with a single dose of 15 Gy and transplanted with cells expressing defined markers.RESULTS: Cells expressing known stem cell markers are localized in the larger ducts of the mouse salivary gland. Isolated cells and cells from day 3 salispheres also express these markers: c-Kit (0.058% vs. 0.65%), CD133 (6% vs. 5%), CD49f (78% vs. 51%), and CD24 (60% vs. 60%, respectively). Intraglandular transplantation of these cells into irradiated salivary glands of mice resulted in stem cell marker-specific recovery of salivary gland function.CONCLUSIONS: Different stem cell-associated markers are expressed in mouse salivary gland cells, which upon transplantation are able to regenerate the irradiation damaged salivary gland.

AB - BACKGROUND: Stem cell therapy could be a potential way for reducing radiation-induced hyposalivation and improving the patient's quality of life. However, the identification and purification of salivary gland stem cells have not been accomplished. This study aims to better characterize the stem/progenitor cell population with regenerative potential residing in the mouse salivary gland.METHODS: Mouse submandibular gland tissue, isolated cells and cultured 3 day old salispheres were tested for their expression of stem cell markers c-Kit, CD133, CD49f, and CD24 using immunohistochemistry for tissue and flow cytometry for cells. Mice were locally irradiated with a single dose of 15 Gy and transplanted with cells expressing defined markers.RESULTS: Cells expressing known stem cell markers are localized in the larger ducts of the mouse salivary gland. Isolated cells and cells from day 3 salispheres also express these markers: c-Kit (0.058% vs. 0.65%), CD133 (6% vs. 5%), CD49f (78% vs. 51%), and CD24 (60% vs. 60%, respectively). Intraglandular transplantation of these cells into irradiated salivary glands of mice resulted in stem cell marker-specific recovery of salivary gland function.CONCLUSIONS: Different stem cell-associated markers are expressed in mouse salivary gland cells, which upon transplantation are able to regenerate the irradiation damaged salivary gland.

KW - AC133 Antigen

KW - Animals

KW - Antigens, CD/metabolism

KW - CD24 Antigen/metabolism

KW - Female

KW - Flow Cytometry

KW - Glycoproteins/metabolism

KW - Head and Neck Neoplasms/radiotherapy

KW - Immunoenzyme Techniques

KW - Integrin alpha6/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Peptides/metabolism

KW - Proto-Oncogene Proteins c-kit/metabolism

KW - Regeneration

KW - Salivary Glands/cytology

KW - Stem Cell Transplantation/methods

KW - Stem Cells/cytology

KW - Xerostomia/etiology

U2 - 10.1016/j.radonc.2011.05.085

DO - 10.1016/j.radonc.2011.05.085

M3 - Journal article

C2 - 21719134

SN - 0167-8140

VL - 99

SP - 367

EP - 372

JO - Radiotherapy & Oncology

JF - Radiotherapy & Oncology

IS - 3

ER -