Protective efficacy of intravenous transplantation of adipose-derived stem cells for the prevention of radiation-induced salivary gland damage.

OBJECTIVE

High-dose radiation therapy in the head and neck area can lead to irreversible damage to salivary glands (SGs) with consequent xerostomia. Adipose-derived stem cells (ADSCs) have been shown to repair or rescue damaged SGs. Thus, we investigated the protective efficacy of ADSCs in the prevention of SG damage induced by high dose radiation.

METHODS

Third-passage ADSCs (1×10(6)) were transplanted by intravenous infusion into the tail-vein of 8-week-old C57BL/6 mice, immediately after local irritation at a dose of 18Gy. The process was repeated twice a week during a period of six consecutive weeks. Eight weeks after radiation, functional evaluations were conducted by measuring salivary flow rate (SFR). Histological, immunohistochemical and transmission electron microscopic (TEM) examinations were performed to analyze microstructural and ultrastructural changes, microvessel density, amylase production, apoptosis, and proliferation activity.

RESULTS

Intravenously administrated ADSCs could home to irradiated SGs within 24h after infusion, significantly increasing SG weights, improving SFR, and preserving the microscopic morphologies of SGs eight weeks post-radiation. More functional acini, higher amylase production levels, and higher microvessel densities were observed in ADSC-treated SGs than in irradiated SGs. Additionally, enhanced cell proliferation activity and reduced radiation-induced SG apoptosis was observed in the ADSC-treated group when compared with the irradiated group.

CONCLUSION

Systemic administration of ADSCs immediately after radiation at a dose of 18Gy can protect both the morphology and function of SGs eight weeks after radiation in mice, and can be used as a protective measure for the prevention of SG damage induced by high-dose radiation.