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.

项目概要/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 迄今为止已开发出的癌症疗法，通常会产生副作用， 对功能结果产生负面影响。辐射引起的软组织损伤的常见并发症 包括皮肤回缩、轮廓畸形、活动受限和伤口不愈合。随着越来越多 因此，预防或减少这些有害的后遗症已成为美国癌症幸存者的数量 成为优先事项。但是，尽管人们对细胞和分子机制的了解有所提高 对于放射后软组织萎缩和纤维化，目前几乎没有有效的治疗选择。最近几年， 脂肪移植已被广泛用于解决癌症切除术后的软组织缺陷问题 放射治疗，尽管脂肪移植解决肿瘤后组织缺陷的有效性可能受到以下因素的限制： 受辐射组织床的纤维炎症变化和血管减少。同时，丰富脂肪 额外的脂肪源性基质细胞可以减少结果变异性并增强脂肪移植物的保留 软组织缺陷的恢复，对于如何发生这种情况的理解仍然存在很大差距。确定如何 补充细胞通过功能亚群分析增强脂肪移植保留可能有助于 开发改进的头颈癌重建治疗方法。自体脂肪移植 还被认为具有再生作用，因为它已被证明可以减轻疼痛和 减少疤痕僵硬，改善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变化仍然未知，但根据我们最近的鉴定 主要负责细胞外基质沉积的位点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，以及如何 发生，可以确定。这些研究的结果将为研究特定的问题开辟新的途径 细胞靶向策略，以减少或预防晚期辐射引起的副作用的发生。总的来说， 提出的实验将全面确定辐射发展的保守机制 纤维化以及脂肪移植如何有效恢复萎缩的放射软组织并改善功能 放射治疗的后遗症。