From the Department of Plastic Surgery, Jichi Medical University.
Departments of Immunology.
Plast Reconstr Surg. 2023 Jun 1;151(6):1207-1216. doi: 10.1097/PRS.0000000000010132. Epub 2023 Jan 2.
Radiation therapy is a mainstay treatment for malignancies, but it can induce deterministic adverse effects in surrounding healthy tissues, including atrophy, fibrosis, ischemia, and impaired wound healing. This exploratory study investigated whether prophylactic administration of products containing adipose tissue-derived stem cells immediately after radiotherapy could prevent the development of long-term functional disorders in irradiated tissues.
A total irradiation dose of 40 Gy (10 Gy, four times weekly) was delivered to the dorsal skin of nude mice. Subsequently, a prophylactic treatment with vehicle, fat tissue, stromal vascular fraction, or micronized cellular adipose matrix was injected subcutaneously into the irradiated area. Six months after these prophylactic treatments, a cutaneous punch wound was created to evaluate histologic changes and wound healing.
Histologic assessments demonstrated dermal thickening, atrophy, and increased collagen deposits in the subcutaneous fatty layer 6 months after radiotherapy. In addition, wound healing was significantly delayed. The prophylactic treatments with three different types of human adipose tissue-derived products significantly prevented radiation-induced histologic changes and accelerated wound healing compared with the vehicle-treated irradiated group.
This is the first study to demonstrate potential for prophylactic treatments after radiotherapy, which could prevent the progression of chronic radiation therapy disorders. The results could have a substantial impact on current anticancer radiotherapies; a next-generation radiation therapy may need to be always combined with a stem cell therapy. Such prophylactic treatments have the potential to improve wound healing of irradiated tissue and clinical outcomes of reconstructive surgery required after cancer radiotherapy.
The results of this study suggest that it is clinically possible to prevent the development of radiation disorders using stem cell therapies. This study may provide a new concept of prophylactic treatment, which would be a paradigm shift in radiotherapy.
放射治疗是治疗恶性肿瘤的主要手段，但它会导致周围健康组织发生确定性不良反应，包括萎缩、纤维化、缺血和伤口愈合受损。本探索性研究旨在调查在放射治疗后立即预防性给予含有脂肪组织源性干细胞的产品是否可以预防照射组织发生长期功能障碍。
将 40 Gy 的总照射剂量（10 Gy，每周 4 次）给予裸鼠背部皮肤。随后，将载体、脂肪组织、基质血管部分或微化细胞脂肪基质预防性地注射到照射区域的皮下。在这些预防性治疗后 6 个月，通过皮肤打孔器创建伤口以评估组织学变化和伤口愈合。
组织学评估显示，放射治疗 6 个月后真皮增厚、萎缩和皮下脂肪层胶原沉积增加。此外，伤口愈合明显延迟。与载体处理的照射组相比，三种不同类型的人脂肪组织源性产品的预防性治疗显著预防了放射诱导的组织学变化并加速了伤口愈合。
这是第一项证明放射治疗后预防性治疗潜力的研究，它可以预防慢性放射治疗障碍的进展。这些结果可能对当前的癌症放射治疗产生重大影响；下一代放射治疗可能需要始终与干细胞治疗相结合。这种预防性治疗有可能改善照射组织的伤口愈合和癌症放射治疗后所需的重建手术的临床结果。
这项研究的结果表明，使用干细胞疗法预防放射障碍的发生在临床上是可行的。本研究可能为预防性治疗提供了一个新概念，这将是放射治疗的范式转变。
