Irradiated head and neck cancer soft tissue reconstruction by fat transfer.

项目摘要/摘要 放射治疗是头颈癌治疗的主要方法，但与其他有效方法一样。 到目前为止已经开发出的癌症治疗方法，它经常与副作用相关，这种副作用可能 对功能结果有负面影响。常见放射性软组织损伤并发症报道 包括皮肤退缩、轮廓畸形、活动受限和无法愈合的伤口。随着不断增加的 美国癌症幸存者的数量，预防或减少这些有害的后遗症 成为当务之急。但尽管对细胞和分子机制的了解有所改善， 对于辐射后软组织萎缩和纤维化，目前几乎没有有效的治疗选择。近年来， 脂肪移植已被广泛用于解决癌症切除和手术后软组织缺失的问题。 放射治疗，尽管脂肪转移解决肿瘤后组织缺陷的有效性可能受到 受照射组织床的纤维炎性改变和血管减少。同时，脂肪的丰富与 额外的脂肪来源的基质细胞可以降低结果的可变性并增强脂肪移植物的保留率 尽管软组织缺失的修复仍然存在很大的差距，但对这一现象如何发生的理解仍存在很大差距。确定如何 补充细胞通过功能亚群分析提高脂肪移植物的保留率 头颈部肿瘤重建的改进治疗方法的发展。自体脂肪移植 也被认为具有再生的作用，因为它已经被证明可以减轻疼痛和 减少疤痕僵硬，改善受辐射损伤皮肤的血管网络和真皮结构。多胖啊 转移改变辐射引起的软组织改变尚不清楚，但根据我们最近的鉴定 主要负责细胞外基质沉积的部位特异性成纤维细胞亚群 对损伤的反应，脂肪转移对这些细胞的分布和特征的影响，以及这是如何 发生了，可以确定。这些研究的发现将为研究特定的 以细胞为靶点的策略，以减少或防止晚期辐射诱导的副作用的发生。总体而言， 提出的实验将全面确定辐射发展的保守机制 纤维化和脂肪转移如何有效地修复萎缩的辐射软组织和改善功能 放射治疗的后遗症。

Project Summary / Abstract Radiation therapy is a mainstay in the treatment of head and neck cancer, but as with all other effective cancer therapies that have been developed to date, it is frequently associated with side effects which can negatively affect the functional outcome. Commonly reported complications of radiation-induced soft tissue injury include skin retraction, contour deformities, restricted movement, and nonhealing wounds. With an increasing number of cancer survivors in the United States, preventing or reducing these detrimental sequelae has thus become a priority. But despite improved knowledge about the cellular and molecular mechanisms responsible for post-irradiation soft tissue atrophy and fibrosis, few effective treatment options currently exist. In recent years, fat grafting has become widely employed to address the soft tissue deficit following cancer resection and radiotherapy, though effectiveness of fat transfer to address post-oncologic tissue deficit may be limited by the fibroinflammatory changes and hypovascularity of the irradiated tissue bed. While, enrichment of fat with additional adipose-derived stromal cells can reduce outcome variability and enhance fat graft retention for restoration of soft tissue deficit, a large gap in understanding how this occurs still exists. Identifying how supplemental cells enhance fat graft retention through functional subpopulation analysis may facilitate development of improved treatment therapies for head and neck cancer reconstruction. Autologous fat transfer has also become recognized to possess a regenerative effect, as it has been shown to decrease pain and stiffness in scars and improve vascular networks and dermal architecture in radiation-damaged skin. How fat transfer alters the soft tissue changes induced by radiation remains unknown, but with our recent identification of site-specific fibroblast subpopulations predominantly responsible for extracellular matrix deposition in response to injury, the effect of fat transfer on the distribution and characteristics of these cells, and how this occurs, can be determined. Findings from these studies would open new avenues for investigation into specific cell-targeted strategies to reduce or prevent onset of late radiation-induced side effects. Collectively, the experiments proposed will comprehensively determine conserved mechanisms for development of radiation fibrosis and how fat transfer can both effectively restore atrophic radiated soft tissue and improve functional sequelae of radiation therapy.