Biomaterials-directed regenerative immunotherapies

生物材料导向的再生免疫疗法

• 批准号: 10023168
• 负责人: JENNIFER H ELISSEEFF
• 金额: $ 114.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10023168
• 关键词: Adaptive Immune System; Aging; Biocompatible Materials; Biological; Blood Vessels; Cells; Cicatrix; Clinic; Clinical; Computational algorithm; Congenital Abnormality; Cues; Development; Disease; Engineering; Foundations; Genomics; Homeostasis; Human; Immune; Immune response; Immune system; Immunity; Immunotherapy; Intervention; Mediating; Molecular; Morphogenesis; Musculoskeletal; Natural regeneration; Pathway interactions; Regenerative Medicine; Role; System; T-Lymphocyte; Therapeutic; Thinking; Tissue Engineering; Tissues; Trauma; cancer immunotherapy; design; engineering design; first responder; healing; improved; innovation; novel; regenerative; repaired; response; scaffold; senescence; standard of care; stem cells; success; therapy design; tissue repair; tissue trauma; tissue-repair responses; tool

Project Summary Tissue loss due to trauma, disease or congenital abnormalities remains an intractable clinical challenge. There are profound deficits in how humans heal and recover from tissue damage and few innovations in regenerative medicine have reached the clinic or improved standard of care. Formation of dysfunctional scar tissue remains the default pathway for repair in the body. The immune system is the first responder to trauma yet this response, and its capacity to orchestrate tissue repair, has been largely ignored. Engineering tissues generally involves combining cells and biomaterial scaffolds with a suite of biological cues to stimulate new tissue development. Until now, these tissue engineering tools have been designed to target stem cells, vascular development, or tissue morphogenesis. Here, we are shifting the focus of tissue engineering design towards direct therapeutic manipulation of the immune system. The remarkable success of cancer immunotherapies highlights how the adaptive immune system is amenable to exquisitely robust intervention and the potential for regenerative immunotherapies. We introduce the concept of regenerative immunotherapies that engage and manipulate the effector class of T cells. Emerging understanding of tissue specific immunity, the role of senescent cells in tissue trauma and repair responses will be combined with our new and unexpected findings on pro-regenerative T cells. Single cell genomic analysis of immune subsets, stromal, and senescent cells combined with novel computational algorithms will be used to develop tissue- specific senescent and immune networks in homeostasis, aging, trauma, and disease. This foundation will serve as the basis for cell and molecular therapy design to enhance T cell mediated pro-regenerative immune responses. While broadly applicable to many tissues, we will first apply regenerative immunotherapies to musculoskeletal tissues before extending to additional tissues. Collectively, these studies will transform traditional thinking of the immune system by re-imagining the immune system as the body’s repair system and use this platform to engineer regeneration.

项目摘要 由于创伤，疾病或先天性异常而导致的组织损失仍然是棘手的临床 挑战。人类如何从组织损伤中康复和恢复有深刻的定义，很少 再生医学的创新已经到达诊所或改进的护理标准。形成 功能失调的疤痕组织仍然是体内修复的默认途径。免疫系统是第一个 对创伤的响应者，但这种反应及其编排组织修复的能力在很大程度上被忽略了。 工程组织通常涉及将细胞和生物材料支架与一套生物线索相结合 刺激新组织的发育。到目前为止，这些组织工程工具旨在针对 干细胞，血管发育或组织形态发生。在这里，我们正在移动组织的焦点 用于直接对免疫系统进行直接治疗操作的工程设计。杰出的成功 癌症免疫疗法强调了自适应免疫系统如何适应性 干预和再生免疫疗法的潜力。我们介绍了再生的概念 接合和操纵T细胞效应子类的免疫疗法。新兴组织的理解 特定的免疫力，感觉细胞在组织创伤和修复反应中的作用将与我们的 促增长T细胞的新发现和意外发现。免疫物种的单细胞基因组分析， 基质和感觉细胞与新型计算算法相结合，将用于发展组织 - 体内平衡，衰老，创伤和疾病的特定感觉和免疫网络。这个基础会 作为细胞和分子疗法设计的基础，以增强T细胞介导的促启动免疫 回答。虽然广泛适用于许多组织，但我们将首先将再生免疫疗法应用于 在扩展到其他组织之前，肌肉骨骼组织。这些研究总的来说会改变 通过将免疫系统重新想象为人体维修系统和 使用此平台来设计再生。