Biomaterial Models of Ancestral Contributions to Wound Healing

祖先对伤口愈合贡献的生物材料模型

• 批准号: 10669283
• 负责人: Erika Michelle Moore
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2023-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10669283
• 关键词: Address; African; African ancestry; Biocompatible Materials; CD34 gene; Cell Communication; Cell model; Cell physiology; Cells; Chronic; Cicatrix; Clinical; Clinical Research; Development; Disease; Environment; European; European ancestry; Extracellular Matrix; Fibrosis; Gene Expression; Genetic; Goals; Growth; Immune; Individual; Inflammation; Injury; Keloid; Measures; Methodology; Modeling; Outcome; Oxidative Stress; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Proteomics; Research; Risk; Site; Tissues; Vision; Work; experience; healing; health disparity; improved; inhibitor; insight; monocyte; progenitor; programs; response; social culture; sociocultural determinant; stem cells; transcriptome sequencing; wound; wound environment; wound healing; wound response

PROJECT ABSTRACT People of African ancestry are 7X more likely to develop overgrowth of scar tissue, or keloids, compared people of European ancestry. Fibrosis, chronic inflammation, and excessive scar formation is dictated by an individual’s ancestral background. Ancestry, quantified in our work through three components of self-identification, genetic ancestry, and sociocultural experiences, informs wound healing. While it is known that ancestry influences clinical wound healing, we do not understand how ancestry influences cell function or cell to cell communication in the wound response. Understanding ancestral contributions to cellular function is critical to interrogate wound healing differences. We hypothesize that ancestry informs differences in cellular response in wound healing. The overall goal of our research program is to leverage biomaterial models to interrogate ancestral contributions in wound healing. In this work, we will interrogate monocyte innate immune cells and CD34+ progenitor stem cells. Our proposed research program will answer three key questions: 1) How does ancestry influence cellular physiology? Preliminary work in our group demonstrates gene expression differences in isolated peripheral blood mononuclear cells comparing self-identified African vs. European descendants. To identify ancestral components beyond self-identification, we will interrogate genetic ancestry and sociocultural factors to quantify ancestry. To determine how each ancestral component influences cell function, we will conduct RNA sequencing and proteomic methodologies in tandem with mechanistic inhibitors to assess cell function differences in monocytes and progenitor stem cells. 2) How does ancestry influence cellular phenotype? While African ancestry is correlated with elevated scar formation, previous clinical studies do not provide mechanistic insights into cellular phenotype that occurs within wound sites. To address this limitation, we will leverage biomaterials and soluble factors to mimic wound extracellular matrix environments. To determine how ancestral components influences the cell phenotype, monocyte and progenitor stem cell responses following culture into the biomaterial microenvironments will be quantified. 3) How does ancestry correlate with the cellular response in wound healing? Wound responses necessitate cell to cell communication. We will utilize biomaterial models of cell-cell interaction and simulate wounding through oxidative stress injury. We will assess how ancestry influences cell to cell communication in these wound environments via genetic and secretome expression. This ESI-MIRA will enable my group to measure the influence of ancestry on wound healing through manipulation of biomaterial platforms. Ultimately, the vision for my lab’s research is to discern the impact of ancestry on wound healing differences and leverage biomaterial models to investigate health disparities in healing.

项目摘要 非洲血统的人是7倍更有可能发展过度生长的疤痕组织，或瘢痕疙瘩，相比之下， 欧洲血统。纤维化、慢性炎症和过度瘢痕形成取决于个体的 祖先背景在我们的工作中，通过自我认同、遗传、 祖先和社会文化经验，告知伤口愈合。虽然我们知道祖先会影响 临床伤口愈合，我们不知道祖先如何影响细胞功能或细胞与细胞的通讯 在伤口反应中。了解祖先对细胞功能的贡献对于询问伤口至关重要 治愈分歧我们假设祖先告知伤口细胞反应的差异 治愈我们的研究计划的总体目标是利用生物材料模型来询问祖先 对伤口愈合的贡献。在这项工作中，我们将询问单核细胞先天免疫细胞和CD 34 + 祖细胞我们提出的研究计划将回答三个关键问题：1）祖先如何 影响细胞生理学？我们小组的初步工作表明， 分离的外周血单核细胞比较自我认定的非洲与欧洲后裔。到 除了自我认同之外，我们还将询问遗传祖先和社会文化 量化祖先的因素。为了确定每个祖先成分如何影响细胞功能，我们将 进行RNA测序和蛋白质组学方法与机制抑制剂串联，以评估细胞 单核细胞和祖细胞的功能差异。2)祖先如何影响细胞 表型？虽然非洲血统与瘢痕形成有关，但以前的临床研究没有发现。 提供了对伤口部位内发生的细胞表型的机械见解。为了解决这一限制， 我们将利用生物材料和可溶性因子来模拟伤口细胞外基质环境。以确定 祖先成分如何影响细胞表型，单核细胞和祖细胞干细胞反应， 将对生物材料微环境中的培养物进行定量。3)祖先是如何与 伤口愈合的细胞反应伤口反应需要细胞与细胞的通讯。我们将利用 细胞-细胞相互作用的生物材料模型和通过氧化应激损伤模拟创伤。我们将评估 祖先如何通过遗传和分泌组影响这些伤口环境中的细胞间通讯 表情这个ESI-MIRA将使我的小组能够通过以下方式来测量祖先对伤口愈合的影响： 生物材料平台的操作。最终，我实验室的研究目标是 伤口愈合差异的祖先，并利用生物材料模型来研究健康 治疗上的差异。