Cell Therapy for Septic Shock

感染性休克的细胞疗法

基本信息

批准号：
7228623
负责人：
DEBORAH Ann BUFFINGTON
金额：
$ 25万
依托单位：
INNOVATIVE BIOTHERAPIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-05-02 至 2007-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7228623
关键词：
Active Biological Transport Acute Acute Kidney Failure Acute Kidney Tubular Necrosis Animal Model Animals Anticoagulation Bacteremia Bacteria Biomedical Engineering Bioreactors Blood Blood Urea Nitrogen Blood flow CAVH Canis familiaris Cardiopulmonary Bypass Cardiovascular system Catheters Cell Survival Cell Therapy Cells Chronic Disease Clinical Clinical Data Clinical Trials Coagulation Process Complex Creatinine Data Deterioration Development Devices Disease Disease Progression Dose Encapsulated Endocrine Endotoxins Equilibrium Evaluation Event Failure Family suidae Fiber Filtration Goals Hemofiltration Histology Homeostasis Hour Human Immunologics In Vitro Infection Injury Intensive Care Units Kidney Kidney Failure Length Life Measures Membrane Metabolic Methodology Modeling Multiple Organ Failure Natural History Organ Outcome Output Pancreatitis Patients Performance Perfusion Phase Plasma Play Prevention Process Property Proteins Pump Rate Recovery Renal function Renal tubule structure Research Personnel Research Proposals Role Safety Sepsis Sepsis Syndrome Septic Shock Series Serum Shock Simulate Site Solid Standards of Weights and Measures Surface Survival Rate Sus scrofa Syndrome System Target Populations Technology Testing Therapeutic Time Tissue Engineering Translating United States Food and Drug Administration Urine Venous Venovenous Hemofiltrations Work base blood perfusion body system clinical application concept cytokine day design hemodynamics improved kidney cell miniaturize mortality novel therapeutics pre-clinical prevent programs research clinical testing research study response scaffold septic size success tissue/cell culture

项目摘要

DESCRIPTION (provided by applicant): Tissue engineering and cell therapy are a new and exciting approach to the treatment of acute and chronic diseases. The potential success of this therapeutic approach lies in the growing appreciation that most disease processes are not due to the lack of a single protein but develop due to alterations in complex interactions of a variety of cell products. Cell therapy is dependent on cell and tissue culture methodologies to expand specific cells to replace important differentiated processes deranged or lost in various disease states. Recent approaches have made progress by placing cells into hollow fiber bioreactors or encapsulating membranes as a means to deliver cell activities to a patient. The systemic inflammatory response syndrome, or SIRS, is a catastrophic sequela of a variety of clinical insults, including infection, pancreatitis, and cardiopulmonary bypass, and claims over forty thousand lives in the U.S. each year. The exceptionally high mortality associated with the syndrome is due in part to the development of the highly lethal multiple system organ failure syndrome (MOF) in a subset of patients with SIRS. The sequential failure of organ systems apparently unrelated to the site of the initial insult has been correlated with altered plasma cytokine levels observed in sepsis. The mortality is especially high in patients with MOF and acute renal failure. This proposal plans experiments to accomplish the following: 1) establish a 10-16 hour model of septic shock in the pig (Specific Aim 1) and 2) to assess the influence of a bioengineered cell based therapeutic device to reverse the progression of the septic disease process (Specific Aim 2) utilizing the 10- 16 hour porcine model. The data accrued in this Phase I program will allow for a proof of concept to justify planned experiments in Phase II to develop a miniature cellular device which will be accessed via an arterial/venous catheter system. At the end of Phase II, the developed pre-clinical data will be used for an IND application for the clinical testing of this therapeutic cellular device in treatment of septic shock. Relevance: The goal of this proposal is to develop a cell based therapy that can be used to reverse the serious clinical events associated with patients who develop septic shock. The success of this project would decrease the very high mortality rate of septic shock and therefore contribute to patient recovery from this devastating disease process.

描述（由申请人提供）：组织工程和细胞疗法是治疗急性和慢性疾病的一种新的令人兴奋的方法。这种治疗方法的潜在成功在于越来越多的欣赏是，大多数疾病过程不是由于缺乏单一蛋白质而导致的，而是由于各种细胞产物复杂相互作用的改变而发展。细胞疗法取决于细胞和组织培养方法，以扩大特定的细胞，以替代在各种疾病状态下破坏或失去的重要分化过程。最近的方法通过将细胞置于空心纤维生物反应器或封装膜作为将细胞活动传递给患者的手段来取得进展。系统性炎症反应综合征（SIRS）是多种临床损伤的灾难性后遗症，包括感染，胰腺炎和心肺旁路，每年在美国有4万次生命。与综合征相关的异常高死亡率部分归因于一部分SIRS患者中高度致命的多重系统器官衰竭综合征（MOF）的发展。器官系统显然与初始侮辱部位无关的顺序故障与败血症中观察到的血浆细胞因子水平改变有关。 MOF和急性肾衰竭患者的死亡率尤其高。该建议计划实验以完成以下操作：1）在猪中建立10-16小时的败血性休克模型（特定目标1）和2）评估基于生物工程的细胞治疗装置的影响，以扭转使用10-16小时猪模型的败血性疾病过程的进展（特定目标2）。在此I阶段计划中所计入的数据将允许概念证明在II阶段中进行计划的实验合理，以开发一种微型蜂窝设备，该设备将通过动脉/静脉导管系统访问。在第二阶段结束时，开发的临床前数据将用于IND应用该治疗性细胞装置治疗败血性休克的临床测试。相关性：该提案的目的是开发一种基于细胞的疗法，该治疗可用于扭转与患病休克的患者相关的严重临床事件。该项目的成功将降低败血性休克的死亡率很高，因此有助于患者从这种毁灭性疾病过程中康复。