Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, 510515, Guangdong, People's Republic of China.
Stem Cell Res Ther. 2024 Sep 27;15(1):324. doi: 10.1186/s13287-024-03904-z.
Chronic radiation dermatitis (CRD) is a late consequence of radiation with high incidence in patients receiving radiotherapy. Conventional therapies often yield unsatisfactory results. Therefore, this study aimed to explore the therapeutic potential and mechanism of adipose-derived stem cells (ADSCs) for CRD, paving the way for novel regenerative therapies in clinical practice.
Clinical CRD skin biopsies were analyzed to character the pathological changes of CRD skin and guided the animal modeling scheme. Subsequently, an in vivo analysisusing mouse CRD models was conducted to explore their effects of ADSCs on CRD, monitoring therapeutic impact for up to 8 weeks. Transcriptome sequencing and histologic sections analysis were performed to explore the potential therapeutic mechanism of ADSCs. Following observing extensive apoptosis of transplanted ADSCs, the therapeutic effect of ADSCs were compared with those of apoptosis-inhibited ADSCs. Multiphoton imaging and analysis of collagen morphologic features were employed to explain how translated ADSCs promote collagen remodeling at the microscopic level based on the contrast of morphology of collagen fibers.
Following injection into CRD-afflicted skin, ADSCs therapy effectively mitigated symptoms of CRD, including acanthosis of the epidermis, fibrosis, and irregular collagen deposition, consistent with the possible therapeutic mechanism suggested by transcriptome sequencing. Notably, in vivo tracking revealed a significant reduction in ADSCs number due to extensive apoptosis. Inhibiting apoptosis in ADSCs partially tempered their therapeutic effects. Mechanically, analysis of collagen morphologic features indicated that translated ADSCs might promote dermal extracellular matrix remodeling through enlarging, lengthening, crimping, and evening collagen, counteracting the atrophy and rupture caused by irradiation.
This study demonstrated that ADSCs underwent substantial apoptosis upon local skin transplantation, and paradoxically, this apoptosis is essential for their efficacy in promoting the regeneration of late radiation-impaired skin. Mechanically, transplanted ADSCs could promote the remodeling and rearrangement of radiation-damaged dermal collagen matrix.
慢性放射性皮炎（CRD）是放疗患者中发生率较高的一种放射后晚期并发症。传统疗法往往效果不佳。因此，本研究旨在探讨脂肪来源干细胞（ADSCs）治疗 CRD 的潜力和机制，为临床实践中的新型再生疗法铺平道路。
分析临床 CRD 皮肤活检以描绘 CRD 皮肤的病理变化，并指导动物建模方案。随后，使用小鼠 CRD 模型进行体内分析，以探讨 ADSCs 对 CRD 的影响，最长可达 8 周进行治疗效果监测。进行转录组测序和组织学切片分析，以探讨 ADSCs 的潜在治疗机制。在观察到大量移植的 ADSCs 凋亡后，将 ADSCs 的治疗效果与凋亡抑制的 ADSCs 进行了比较。采用多光子成像和胶原形态特征分析，根据胶原纤维形态的对比，从微观水平解释了转译的 ADSCs 如何促进胶原重塑。
将 ADSCs 注射到 CRD 受累皮肤后，ADSCs 治疗有效地减轻了 CRD 的症状，包括表皮的棘皮病、纤维化和不规则的胶原沉积，这与转录组测序提示的可能治疗机制一致。值得注意的是，体内追踪显示由于广泛的凋亡，ADSCs 的数量显著减少。抑制 ADSCs 的凋亡部分减弱了它们的治疗效果。从机械角度分析胶原形态特征表明，转译的 ADSCs 可能通过扩大、延长、卷曲和均匀化胶原来促进真皮细胞外基质的重塑，从而抵消辐射引起的萎缩和破裂。
本研究表明，ADSCs 在局部皮肤移植后发生大量凋亡，而矛盾的是，这种凋亡对于它们促进晚期放射性损伤皮肤再生的疗效至关重要。从机械角度来看，移植的 ADSCs 可以促进受损真皮胶原基质的重塑和重排。
