Zhijin Li1, Yan Wang1, Hongyan Xing2, Zhifa Wang1, Hanqing Hu1, Ran An3, Haiyan Xu3, Yanpu Liu4, Bin Liu5. 1. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China. 2. Department of Stomatology, Xinzhou 2nd People's Hospital, 120 Yong Xing Nan Road, Xinzhou, Shanxi Province 034100, PR China. 3. State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China. 4. State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: liuyanpu@fmmu.edu.cn. 5. State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: kqyljd_liu@126.com.
Abstract
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.
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.
Authors: Primož Strojan; Katherine A Hutcheson; Avraham Eisbruch; Jonathan J Beitler; Johannes A Langendijk; Anne W M Lee; June Corry; William M Mendenhall; Robert Smee; Alessandra Rinaldo; Alfio Ferlito Journal: Cancer Treat Rev Date: 2017-07-18 Impact factor: 12.111