Yoshizumi Kayo, Saito Natsumi, Wu Yunyan, Shirado Takako, Asahi Rintaro, Mori Masanori, Yamamoto Yoshihiro, Sowa Yoshihiro, Yoshimura Kotaro
From the Department of Plastic Surgery, Jichi Medical University, Tochigi, Japan.
Plast Reconstr Surg Glob Open. 2025 Jan 27;13(1):e6419. doi: 10.1097/GOX.0000000000006419. eCollection 2025 Jan.
The pathogenesis of deterministic radiation damage is not clearly understood, but it has been reported that fibroinflammatory pathways are up-regulated. We hypothesized that the number of adipose-derived stem/stromal cells (ASCs) decline after radiotherapies, preventing normalization of fibrosis and angiogenesis, resulting in chronic radiation damages that progress over time.
Dorsal skin of 8-week-old male BALB/cfC3H mice was irradiated with 10 Gy weekly for 4 weeks. At 1, 3, 6, 9, and 12 months after radiotherapy (n = 5, 5, 5, 5, and 4), tissue hemoglobin oxygen saturation, and time until epithelialization were evaluated. Skin biopsies were measured for thickness and CD34/isolectin stem/stromal cell count. Nonirradiated (NRT) controls were evaluated at each time point as well (n = 5 each).
Compared with NRT controls, time until epithelialization was significantly longer at 1 month (28 ± 3, < 0.01); not statistically different at 3 months (16 ± 2, = 0.32); and lengthened over time at 6 months (20 ± 2, = 0.21), 9 months (28 ± 2, < 0.01), and 12 months (26 ± 3, < 0.01), as did tissue oxygen saturation. The number of CD34/isolectin ASCs decreased over time, at 1 month (5.3 ± 1.3, = 0.01), 3 months (6.0 ± 1.4, = 0.03), 6 months (4.0 ± 0.8, < 0.01), 9 months (1.7 ± 0.5, < 0.01), and 12 months (0.3 ± 0.5, < 0.01). The subcutaneous fatty layer was significantly thinner at 3 months (116 ± 33, < 0.01), 6 months (147 ± 22, = 0.02), 9 months (52 ± 12, = 0.04), and 12 months (89 ± 19, = 0.04), but not at 1 month (141 ± 18, = 0.43).
After 6 months postirradiation, the number of ASCs continued to decline over time, accompanied by irreversible progression of fibrosis, atrophy, and ischemia, which resulted in impaired wound healing.
确定性辐射损伤的发病机制尚不清楚，但有报道称纤维炎症通路被上调。我们推测，放疗后脂肪来源的干/基质细胞（ASC）数量减少，阻碍了纤维化和血管生成的正常化，导致慢性辐射损伤随时间进展。
对8周龄雄性BALB/cfC3H小鼠的背部皮肤每周照射10 Gy，共照射4周。在放疗后1、3、6、9和12个月（n分别为5、5、5、5和4），评估组织血红蛋白氧饱和度以及上皮化所需时间。对皮肤活检样本测量厚度并计数CD34/异凝集素干/基质细胞数量。在每个时间点也对未照射（NRT）的对照组进行评估（每组n = 5）。
与NRT对照组相比，上皮化所需时间在1个月时显著延长（28 ± 3，P < 0.01）；3个月时无统计学差异（16 ± 2，P = 0.32）；6个月（20 ± 2，P = 0.21）、9个月（28 ± 2，P < 0.01）和12个月（26 ± 3，P < 0.01）时随时间延长，组织氧饱和度情况相同。CD34/异凝集素ASC数量随时间减少，在1个月时（5.3 ± 1.3，P = 0.01）、3个月时（6.0 ± 1.4，P = 0.03）、6个月时（4.0 ± 0.8，P < 0.01）、9个月时（1.7 ± 0.5，P < 0.01）和12个月时（0.3 ± 0.5，P < 0.01）。皮下脂肪层在3个月（116 ± 33，P < 0.01）、6个月（147 ± 22，P = 0.02）、9个月（52 ± 12，P = 0.04）和12个月（89 ± 19，P = 0.04）时显著变薄，但在1个月时无变化（141 ± 18，P = 0.43）。
放疗后6个月，ASC数量随时间持续下降，同时伴有纤维化、萎缩和缺血的不可逆进展，导致伤口愈合受损。
