Jin Im Geon, Kim Jin Ho, Wu Hong-Gyun, Hwang Soon Jung
1Department of Oral & Maxillofacial Surgery, School of Dentistry, Brain Korea 21 Plus, Dental Research Institute, Seoul National University, Seoul, Korea.
2Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea.
Tissue Eng Regen Med. 2016 Feb 2;13(1):78-90. doi: 10.1007/s13770-015-0055-x. eCollection 2016 Feb.
Radiation-induced skin ulceration is a frequent complication of radiation therapy. This study investigated the effects of rat mesenchymal stem cells (rMSCs) and platelet-derived growth factor (PDGF) on the healing of radiation-induced soft tissue injury. Sprague-Dawley rats (n=17) were irradiated on the right and left buttocks with a single dose of 50 Gy. The right buttocks were administered with phosphatebuffered solution as a control. The left buttocks were administered with either rMSCs (2×10 cells), PDGF (8 µg), or PDGF combined with rMSCs. Administration was done at three weeks after irradiation. Wound healing was analyzed by calculating the percentage of residual ulcerated skin area compared to the total irradiated area during the five week healing period after administration. Modified skin scores were also assessed. Finally, skin lesions were histologically evaluated. More than 40% of the irradiated skin area within the irradiated zone underwent ulceration within 16 days postirradiation, with peak ulceration exceeding 50% around three weeks post-irradiation. Administration of rMSCs or PDGF alone did not confer any significant healing effect. The combined rMSCs+PDGF treatment significantly reduced the wound size compared with the nontreated control up to two weeks postinjection. Regarding the histological examination, lesions administered with PDGF (either alone or mixed with rMSCs) resulted in a greater deposition of highly organized collagen fibers throughout the dermis layer, compared with the control. In conclusion, the combined administration of rMSCs and PDGF efficiently enhanced the healing of radiation-induced skin ulceration.
放射性皮肤溃疡是放射治疗常见的并发症。本研究调查了大鼠间充质干细胞(rMSCs)和血小板衍生生长因子(PDGF)对放射性软组织损伤愈合的影响。将17只Sprague-Dawley大鼠的左右臀部单次照射50 Gy。右侧臀部给予磷酸盐缓冲溶液作为对照。左侧臀部给予rMSCs(2×10个细胞)、PDGF(8μg)或PDGF与rMSCs联合使用。给药在照射后三周进行。通过计算给药后五周愈合期内残留溃疡皮肤面积占总照射面积的百分比来分析伤口愈合情况。还评估了改良的皮肤评分。最后,对皮肤病变进行组织学评估。照射区域内超过40%的照射皮肤面积在照射后16天内发生溃疡,溃疡高峰期在照射后三周左右超过50%。单独给予rMSCs或PDGF没有任何显著的愈合效果。与未治疗的对照组相比,rMSCs+PDGF联合治疗在注射后两周内显著减小了伤口大小。关于组织学检查,与对照组相比,给予PDGF(单独或与rMSCs混合)的病变在整个真皮层导致高度有序的胶原纤维沉积增加。总之,rMSCs和PDGF联合给药有效地促进了放射性皮肤溃疡的愈合。