Fujita Kazutoshi, Nishimoto Soh, Fujiwara Toshihiro, Sotsuka Yohei, Tonooka Maki, Kawai Kenichiro, Kakibuchi Masao
Department of Plastic Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
PLoS One. 2017 Sep 8;12(9):e0184534. doi: 10.1371/journal.pone.0184534. eCollection 2017.
Radiation is an important therapy for cancer with many benefits; however, its side effects, such as impaired wound healing, are a major problem. While many attempts have been made to overcome this particular disadvantage, there are few effective treatments for impaired wound healing in an X-ray-irradiated field. One reason for this deficiency is the lack of experimental models, especially animal models. We have previously reported a mouse model of impaired wound healing in which the irradiation area was restricted to the hindlimbs. In this mouse model, due to the size of the animal, a diameter of five millimeters was considered the largest wound size suitable for the model. In addition, the transplanted cells had to be harvested from other inbred animals. To investigate larger wounds and the impact of autologous specimen delivery, a rabbit model was developed. Rabbits were kept in a special apparatus to shield the body and hindlimbs while the irradiation field was exposed to radiation. Six weeks after irradiation, a 2 x 2 cm, full-thickness skin defect was made inside the irradiation field. Then, the wound area was observed over time. The wound area after irradiation was larger than that without irradiation at all time points. Both angiogenesis and collagen formation were reduced. For further study, as an example of using this model, the effect of autologous platelet-rich plasma (PRP) was observed. Autologous PRP from peripheral blood (pb-PRP) and bone marrow aspirate (bm-PRP) was processed and injected into the wounds in the irradiated field. Two weeks later, the wounds treated with bm-PRP were significantly smaller than those treated with phosphate buffer vehicle controls. In contrast, the wounds treated with pb-PRP were not significantly different from the controls. This rabbit model is useful for investigating the mechanism of impaired wound healing in an X-ray-irradiated field.
放射治疗是癌症治疗的重要手段,具有诸多益处;然而,其副作用,如伤口愈合受损,却是一个重大问题。尽管人们已多次尝试克服这一特殊劣势,但针对X射线照射区域伤口愈合受损的有效治疗方法却寥寥无几。造成这种不足的一个原因是缺乏实验模型,尤其是动物模型。我们之前报道过一种伤口愈合受损的小鼠模型,其中照射区域仅限于后肢。在这个小鼠模型中,由于动物体型的原因,五毫米的直径被认为是适合该模型的最大伤口尺寸。此外,移植细胞必须从其他近交系动物身上获取。为了研究更大的伤口以及自体标本递送的影响,我们开发了一种兔模型。兔子被置于一个特殊装置中,在照射时屏蔽身体和后肢,仅暴露照射区域。照射六周后,在照射区域内制造一个2×2厘米的全层皮肤缺损。然后,随时间观察伤口面积。在所有时间点,照射后的伤口面积均大于未照射的伤口面积。血管生成和胶原蛋白形成均减少。作为使用该模型的一个例子,为了进一步研究,观察了自体富血小板血浆(PRP)的效果。从外周血(pb-PRP)和骨髓抽吸物(bm-PRP)中提取的自体PRP经过处理后注入照射区域的伤口。两周后,接受bm-PRP治疗的伤口明显小于接受磷酸盐缓冲液载体对照治疗的伤口。相比之下,接受pb-PRP治疗的伤口与对照组无显著差异。这种兔模型对于研究X射线照射区域伤口愈合受损的机制很有用。