Therapeutic effects of human umbilical cord–derived mesenchymal stem cells on canine radiation-induced lung injury

Publication date: Available online 6 June 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Yuhui Hao, Yonghong Ran, Binghui Lu, Jiayin Li, Jiaojiao Zhang, Chunjing Feng, Jinhui Fang, Ruoyu Ma, Zhihui Qiao, Xiaotian Dai, Wei Xiong, Jing Liu, Qi Zhou, Jie Hao, Rong Li, Jianwu Dai
ObjectiveTo investigate the effect of human umbilical cord–derived mesenchymal stem cell (MSC) transplantation on canine radiation-induced lung injury.MethodsBeagle dogs received localized 15-Gy radiation to the right lower lung from X-rays to establish the model of radiation-induced lung injury. After 180 days, dogs were divided into two groups (4/ group). The MSC group received intratracheal MSC transplantation, and the saline group received the same volume of normal saline by lavage. The effect of MSC transplantation on lung injury was then evaluated during 180 days after transplantation.ResultsAt 180 days after 15-Gy radiation, canine arterial blood oxygen partial pressure was significantly decreased, and the levels of hydroxyproline and transforming growth factor-β (TGF-β) in peripheral blood were significantly increased, whereas that of TGF-α was significantly decreased. Computed tomography (CT) evaluation revealed visible honeycomb shadows in the right middle and lower pulmonary pleurae. Then, the blood oxygen partial pressure of the MSC group gradually increased over time, whereas the levels of hydroxyproline and TGF-β in the peripheral blood showed a decreasing trend, and TGF-α levels gradually increased, which differed significantly from the results observed in the saline group. In addition, CT and pathological examination showed that the degree of lung injury in the MSC group was milder. The MSC group also showed significantly increased pulmonary superoxide dismutase levels and significantly decreased TNF-α, IL-1, and hyaluronic acid levels. Further study confirmed that MSC transplantation inhibited the activation of TGF-β/Smad2/3 in lung tissues, and in vitro experiments showed that medium conditioned with MSCs effectively inhibited the increase in Smad2/3 levels induced by TGF-β1.ConclusionCanine radiation-induced lung injury could be observed at 180 days after radiation at 15 Gy. MSC transplantation can reduce oxidative stress, inflammatory reactions, and TGF-β/Smad2/3 pathway activation, thereby reducing lung injury.

Teaser

Radiation-induced lung injury is a common complication following radiotherapy for thoracic tumours. Our studies show that canine radiation-induced lung injury could be observed at 180 days after X-ray radiation at 15 Gy, and intratracheal mesenchymal stem cell (MSC) transplantation can reduce oxidative stress, inflammatory reactions, and TGF-β/Smad2/3 pathway activation, thereby reducing lung injury. This finding provides a basis for the application of MSCs in clinical transplantation therapies for radiation-induced lung injury.


https://ift.tt/2M5QbOk