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: 10887281
• 负责人: Erika Michelle Moore
• 金额: $ 37.43万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10887281
• 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 非洲祖先的人的疤痕组织过度生长或keloids的可能性更高。 欧洲血统。纤维化，慢性炎症和多余的疤痕形成取决于个人的 祖先背景。祖先，在我们的工作中通过自我识别的三个组成部分进行量化 祖先和社会文化经验可为伤口康复提供信息。众所周知，祖先的影响 临床伤口愈合，我们不了解祖先如何影响细胞功能或细胞对细胞通信的影响 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 治愈差异。我们假设祖先为伤口中细胞反应的差异提供了差异 康复。我们研究计划的总体目标是利用生物材料模型来审问祖先 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电池和CD34+ 祖细胞细胞。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？我们小组的初步工作证明了基因表达差异 分离的外周血单核细胞比较了自我认同的非洲与欧洲后代。到 确定超出自我认同的祖先组成部分，我们将审问遗传血统和社会文化 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 在与机械抑制剂同时进行RNA测序和蛋白质组学方法来评估细胞 单核细胞和祖细胞的功能差异。 2）祖先如何影响细胞 表型？尽管非洲血统与疤痕形成升高相关，但以前的临床研究却不 提供对伤口部位内发生的细胞表型的机械见解。为了解决这个限制， 我们将利用生物材料和实心因素来模仿伤口细胞外基质环境。确定 祖先成分如何影响细胞表型，单核细胞和祖细胞细胞反应 将量化生物材料微环境的培养。 3）祖先与 伤口愈合中的细胞反应？伤口反应需要细胞对细胞通信的必要细胞。我们将利用 细胞 - 细胞相互作用的生物材料模型，并模拟流经氧化应激损伤的逻辑。我们将评估 祖先如何通过遗传和分泌组在这些伤口环境中影响细胞与细胞通信 表达。这个Esi-Mira将使我的小组能够测量血统对通过 操纵生物材料平台。最终，我实验室研究的愿景是辨别影响 祖先在伤口愈合差异和利用生物材料模型来研究健康 康复的差异。

项目成果

Ancestry of cells must be considered in bioengineering.

在生物工程中必须考虑细胞的祖先。

• DOI: 10.1038/s41578-021-00397-7
• 发表时间: 2022
• 期刊: Nature reviews. Materials
• 作者: Moore,Erika;Allen,JosephineB;Mulligan,ConnieJ;Wayne,ElizabethC
• 通讯作者: Wayne,ElizabethC