Novel Strategies to Improve Blood Transfusion Practice

改善输血实践的新策略

• 批准号: 10494380
• 负责人: Hongbo R Luo
• 金额: $ 265.54万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 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 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494380
• 关键词: Adopted; Affect; Area; Autologous Transplantation; Bacterial Infections; Biology; Blood Cells; Blood Platelets; Blood Transfusion; Blood Vessels; Bone Marrow; Bone Marrow Diseases; Bone Marrow Transplantation; Bone marrow failure; Cell Death Signaling Process; Cell Therapy; Cells; Cessation of life; Clinical; Collaborations; Cryopreservation; Cytometry; Defect; Effectiveness; Endocytosis; Engraftment; Ensure; Erythrocyte Transfusion; Erythrocytes; Functional disorder; Gene-Modified; Glues; Goals; Half-Life; Hematological Disease; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hemorrhage; Image; Infection; Intervention; Investigation; Knowledge; Lead; Lesion; Medical; Membrane; Metabolic; Modernization; Molecular; Mycoses; Neutropenia; Outcome; Pathway interactions; Patients; Pharmacology; Platelet Transfusion; Preparation; Procedures; Process; Productivity; Program Research Project Grants; Public Health; RHOA gene; Reagent; Recording of previous events; Regimen; Regulation; Research; Research Project Grants; Role; Sickle Cell Anemia; Signal Transduction; Specialist; Sum; Supporting Cell; Thrombocytopenia; Transfusion; Transplant Recipients; Transplantation; United States National Institutes of Health; Vesicle; allotransplant; blood product; clinical efficacy; cohesion; cost effectiveness; design; experience; experimental study; granulocyte; hematopoietic cell transplantation; improved; individualized medicine; innovation; insight; multidisciplinary; neutrophil; novel; novel strategies; novel therapeutic intervention; prevent; programs; response; synergism; trafficking; transfusion medicine; virtual

Project Summary Optimizing blood cell support for specific patient groups and clinical settings is an emerging priority in transfusion medicine. Patients undergoing hematopoietic cell transplantation (HCT) require significant transfusion support (including red blood cells, platelets, and granulocytes) because of the transplant-related bone marrow (BM) dysfunction state. However, challenges and shortcomings still exist for modern transfusion practices in the peri-transplant setting, limiting their clinical efficacy and cost effectiveness. Mechanisms underlying the effect and effectiveness of blood transfusion in the peri-transplant setting are important, understudied, and poorly understood, representing a critical gap in our biomedical knowledge. A coordinated, multi-disciplinary P01 program project on such mechanisms is warranted, considering the medical and public health significance of blood transfusion and cellular therapies, and will be innovative, constituting a distinct area of investigation in the current NIH portfolio. The long-term thematic objective of this research program is to provide more effective transfusion support for HCT recipients by better understanding the molecular and cellular mechanisms underlying the effect and effectiveness of blood transfusion in the peri-transplant setting. Drs. John Manis, Leslie Silberstein, and Shin-Young Park (Project 1) will elucidate the dynamic relationship between BM niche and HSPC in sickle cell disease (SCD) patients, specifically hypothesizing that insight into how BM vascular and perivascular niches are distorted in SCD and restored by RBC transfusion shall lead to opportunities for targeted intervention in HSC transplantation in SCD patients. Drs. Hongbo Luo and Li Chai (Project 2) will study cell death signaling in granulocyte transfusion (GTX), specifically hypothesizing that GTX can be improved by simultaneously targeting multiple death pathways. This study will assist us to design novel therapeutic strategies for improving the efficacy of GTX and combating neutropenia-related infections in the peri-transplant period. Drs Jose Cancelas and Yi Zheng (Project 3) will focus on platelet transfusion which is commonly used to prevent or treat bleeding in thrombocytopenic patients, including HCT recipients. The goal is to elucidate the role of RHOA/RAC1 signaling in cold storage-induced clearance of platelets and to design novel clinical procedures (e.g. pharmacological inhibition of RHOA) for the long-term storage and application of platelets in transfusion medicine. The 3 research projects will be bolstered by a unique Cytometry and Imaging Core, led by Dr. Shin-Young Park, to maximize efficiency, economy, and productivity. An Administrative Core will coordinate the activities of these projects and cores to form a cohesive whole. The overall scientific synergy of ideas, reagents and expertise afforded by the multiple collaborations shall enable this Program Project to advance our understanding of the biology of blood transfusion, and to apply findings made toward enhancing the effectiveness of modern-day blood transfusion therapy for specific patient groups in the peri-transplant setting.

项目摘要 优化针对特定患者组和临床环境的血细胞支持是新兴的优先级 输血医学。接受造血细胞移植（HCT）的患者需要显着 由于移植相关的输血支持（包括红细胞，血小板和粒细胞） 骨髓（BM）功能障碍状态。但是，现代输血仍然存在挑战和缺点 在移植物周围环境中的实践，限制了它们的临床功效和成本效益。机制 在移植周围环境中输血的效果和有效性是重要的，很重要， 在我们的生物医学知识上进行了研究且知之甚少，这代表了一个危险的差距。协调， 考虑到医疗和公众 输血和细胞疗法的健康意义，并且将具有创新性，构成一个独特的 当前NIH投资组合中的调查领域。该研究计划的长期主题目标是 通过更好地了解分子和 在移植物周围环境中输血的效果和有效性的基础的细胞机制。 博士。约翰·曼尼斯（John Manis），莱斯利·西尔伯斯坦（Leslie Silberstein）和新杨公园（项目1）将阐明动态关系 在镰状细胞疾病（SCD）患者中的BM利基市场和HSPC之间，特别假设该洞察力 BM血管和血管周期壁ches如何在SCD中扭曲并被RBC输血恢复 在SCD患者中有针对性干预HSC移植的机会。博士。 Hongbo Luo和Li Chai （项目2）将研究粒细胞输血（GTX）中的细胞死亡信号传导，特别是假设GTX 可以通过同时靶向多个死亡途径来改善。这项研究将帮助我们设计小说 改善GTX疗效并打击中性粒细胞减少相关感染的治疗策略 移植期。 Jose Cancutas博士和Yi Zheng（项目3）将重点关注血小板输血 通常用于预防或治疗血小板减少患者（包括HCT接受者）的出血。目标是 阐明Rhoa/Rac1信号传导在冷藏引起的血小板清除率中的作用并设计 新型临床程序（例如，RHOA的药理学抑制），用于长期存储和应用 输血医学中的血小板。这三个研究项目将通过独特的细胞仪和 由Shin-Young Park博士领导的成像核心，以最大程度地提高效率，经济性和生产力。一个 行政核心将协调这些项目和核心的活动，以形成整体。这 多次合作提供的思想，试剂和专业知识的总体科学协同作用应实现 这个计划项目旨在提高我们对输血生物学的理解，并应用发现 旨在增强特定患者组的现代输血疗法的有效性 在移植植物环境中。