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.


CONCLUSIONS
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.
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Zhijin
Z
Li
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Yan
Y
Wang
Department of Stomatology, Xinzhou 2nd People's Hospital, 120 Yong Xing Nan Road, Xinzhou, Shanxi Province 034100, PR China.
Hongyan
H
Xing
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Zhifa
Z
Wang
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Hanqing
H
Hu
State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Ran
R
An
State Key Laboratory of Military Stomatology, Laboratory Animal Center, School of Stomatology, Fourth Military Medical University, Xi'an 710032, PR China.
Haiyan
H
Xu
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.
Yanpu
Y
Liu
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.
Bin
B
Liu
D061354:Acinar Cells / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000637:transplantation*; D000273:Adipose Tissue / Q000166:cytology*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy*; D011897:Random Allocation; D012469:Salivary Glands / Q000473:pathology* / Q000528:radiation effects*; D033581:Stem Cell Transplantation / Q000379:methods*
D000681:Amylases
Adipose-derived stem cells; Cell therapy; Radiation injuries; Salivary gland