New Generation Blood Exchange Devices for Enhancing Tissue Regeneration and Health

用于增强组织再生和健康的新一代血液交换装置

• 批准号: 9906269
• 负责人: Kiana Aran
• 金额: $ 38.54万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-21 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906269
• 关键词: Age; Anastomosis - action; Animal Experimentation; Animals; Attenuated; Autoimmune Diseases; Back; Biological Assay; Blood; Blood Circulation; Blood Component Removal; Brain; Brain Diseases; Cell Separation; Cells; Cognition; Degenerative Disorder; Devices; Disease; Dose; Endocrine; Engineering; Environment; Excision; FDA approved; Fetal Erythroblastosis; Generations; Germ Layers; Goals; Health; Hippocampus (Brain); Human; IL6 gene; Inflammation; Inflammatory; Joints; Learning; Leukocytes; Liver; Maintenance; Mammals; Measures; Modality; Mus; Muscle; Natural regeneration; Operative Surgical Procedures; Organ; Outcome; Parabiosis; Pathology; Performance; Plasma; Procedures; Production; Proteins; Publishing; Sickle Cell Anemia; System; TNF gene; Therapeutic; Tissues; Transfusion; Work; aged; cell age; combat; cytokine; improved; in vivo; inhibitor/antagonist; myogenesis; neurogenesis; next generation; repaired; tissue regeneration

Exchange transfusion (apheresis) is a routine strategy for the management of several diseases, such as sickle cell disease, hemolytic disease of newborns, autoimmune disorders, etc. Interestingly, the body of published work on heterochronic parabiosis, the surgical joining of two animals of different ages, and more recently, our study on heterochronic blood exchange, suggest that blood apheresis can be repositioned and used as a new modality: restoring the circulatory environment of aged mammals back to a productive, young, composition, may help to rapidly and broadly enhance the maintenance and repair of multiple organs, combatting a number of degenerative diseases of brain, muscle, liver, etc. and inflammatory disorders. In contrast to the permanent anastomosis of parabiosis, in our small animal blood exchange system animals are connected and disconnected at will, removing the influence of shared organs, adaptation to being joined, etc. Unlike parabiosis, where joint circulation is stochastically established in ~7-10 days, our procedure is less invasive and accurately controlled, the exchange volumes are easily programmed and measured; and the onset and duration of the effects can be accurately and with ease interrogated. The cells versus plasma heterochronicity can be studied and immuno-affinity modules enable removal of specific inhibitory molecules from the old circulation prior to return of such “rejuvenated” blood into the old animal; as well as a screen for candidate systemic proteins, removal of which from young circulation inhibits tissue maintenance and repair. We will (1) determine the onset and duration of the effects of heterochronic blood apheresis on health and maintenance of muscle, liver and brain, animal performance (strength and cognition), and systemic cytokine profile, also defining the minimal functional dose of exchanged blood that significantly influence these parameters; (2) engineer the V2 device where, in continuous apheresis between two animals of different age, circulating leukocytes are separated from plasma, studying how a cross-match of the age of cells and plasma influences tissue maintenance and repair; (3) engineer the V3 device with imunoaffinity modules allowing to screen and attenuate to young – healthy levels candidate systemic proteins, using IL6 and TNF-a as the first candidates, that when elevated with age have negative effects on tissue health and regeneration.

交换输血（格言）是管理多种疾病的常规策略，例如 镰状细胞疾病，新生儿的溶血疾病，自身免疫性疾病等。有趣的是， 发表的有关异核核病的工作，两种不同年龄的动物的外科手术连接以及更多 最近，我们关于异缘血液交换的研究表明，血液上可以重新定位，并且 用作一种新方式：恢复老年哺乳动物的电路环境回到富有成效的年轻， 组成，可能有助于快速，广泛地增强多个器官的维护和维修， 打击大脑，肌肉，肝脏等多种退化性疾病。 在我们的小动物血液交换系统中，与抛物线抗性的永久吻合相反 随意连接和断开动物，消除了共享器官的影响，适应了 加入等。与副降压片不同，在〜7-10天内，联合循环随机循环建立 侵入性较低和准确控制，交换量易于编程和测量；和 效果的发作和持续时间可以准确，轻松审问。细胞与血浆 杂音性可以进行研究，免疫亲和力模块可以去除特定的抑制分子 从旧的循环中，在将这种“复兴”的血液返回到旧动物之前；以及屏幕 候选全身蛋白质，从Young循环中去除的蛋白质会抑制组织的维持和修复。 我们将（1）确定异缘血液检查对健康的影响和持续时间 维持肌肉，肝脏和大脑，动物表现（力量和认知）以及全身细胞因子 剖面，还定义了交换的血液的最低功能剂量，从而显着影响这些 参数; （2）工程师的V2设备，在两种不同年龄的动物之间的连续分离中， 循环白细胞与血浆分离，研究细胞和血浆年龄如何 影响组织维护和修复； （3）工程师的V3设备，具有不可分割的模块，可以 屏幕并衰减年轻 - 健康水平候选全身蛋白，使用IL6和TNF-A作为第一个 候选人，随着年龄的增长，对组织健康和再生会产生负面影响。