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

通过脂肪移植进行辐照头颈癌软组织重建。

• 批准号: 10403603
• 负责人: MICHAEL T LONGAKER
• 金额: $ 37.16万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10403603
• 关键词: Abdomen; Address; Adipose tissue; Angiogenic Factor; Architecture; Articular Range of Motion; Atrophic; Autologous; Beds; Biological Assay; Biology; Blood Vessels; CD34 gene; Cancer Survivor; Cell surface; Cells; Characteristics; Chromatin; Chronic; Cicatrix; Contracture; Defect; Deformity; Deposition; Dermal; Dermis; Development; Dorsal; ENG gene; Effectiveness; Embryo; Environment; Evaluation; Excision; Extracellular Matrix; Fatty acid glycerol esters; Fibroblasts; Fibrosis; Flow Cytometry; Gene Expression; Graft Survival; Harvest; Head and Neck Cancer; Histologic; Homeobox; Investigation; Knowledge; Limb structure; Malignant Neoplasms; Modeling; Modernization; Molecular; Movement; Mus; Outcome; PECAM1 gene; PTPRC gene; Pain; Pathway interactions; Patients; Platelet-Derived Growth Factor alpha Receptor; Process; Production; Proliferating; Quality of life; Radiation; Radiation Fibrosis; Radiation induced damage; Radiation therapy; Radiation-Induced Change; Reporter; Reporting; Role; Scalp structure; Signal Transduction; Site; Skin; Soft Tissue Injuries; Stromal Cells; Surface; Techniques; Tissues; United States; base; cancer therapy; cytokine; effective therapy; experimental study; fat grafting; functional outcomes; improved; irradiation; lipid biosynthesis; negative affect; neovascular; non-healing wounds; novel strategies; prevent; profibrotic cytokine; radiation effect; reconstruction; regenerative; response; response to injury; restoration; side effect; skin damage; soft tissue; tissue reconstruction; tissue regeneration; transcriptome; type IA bone morphogenetic protein receptor; vasculogenesis

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.

项目总结/摘要 放射治疗是治疗头颈癌的主要手段，但与所有其他有效的治疗方法一样， 迄今为止已经开发的癌症治疗，它经常与副作用有关， 对功能结果产生负面影响。放射性软组织损伤的常见并发症 包括皮肤退缩、轮廓畸形、运动受限和不愈合伤口。随着越来越 美国癌症幸存者的数量，预防或减少这些有害的后遗症，因此， 成为优先事项。但是，尽管有关细胞和分子机制的知识有所提高， 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后的软组织缺损， 放射治疗，虽然脂肪转移解决肿瘤后组织缺损的有效性可能会受到限制， 纤维炎性变化和照射组织床的血管减少。而富含脂肪的 额外的脂肪来源的基质细胞可以减少结果的变异性， 尽管目前还不清楚如何修复软组织缺损，但在理解这是如何发生的方面仍然存在很大的差距。确定如何 通过功能亚群分析增加脂肪移植物保留的补充细胞可以促进 开发改进的头颈癌重建治疗方法。自体脂肪转移 也被认为具有再生作用，因为它已被证明可以减少疼痛， 改善辐射损伤皮肤血管网络和真皮结构。多胖 转移改变了辐射引起的软组织变化仍然是未知的，但随着我们最近的鉴定 的位点特异性成纤维细胞亚群主要负责细胞外基质沉积， 对损伤的反应，脂肪转移对这些细胞的分布和特征的影响，以及这是如何发生的。 发生，可以确定。这些研究的结果将为研究特定的 细胞靶向策略，以减少或预防晚期辐射诱导的副作用的发生。统称 提出的实验将全面确定辐射发展的保守机制 纤维化以及脂肪转移如何有效恢复萎缩辐射软组织并改善功能 放射治疗的后遗症