Cell Therapy for Septic Shock

描述（申请人提供）：组织工程和细胞治疗是一种新的和令人兴奋的治疗急慢性疾病的方法。这种治疗方法的潜在成功在于人们越来越认识到，大多数疾病过程不是由于缺乏单一蛋白质，而是由于各种细胞产物的复杂相互作用的改变而发展的。细胞治疗依赖于细胞和组织培养方法来扩增特定细胞，以取代在各种疾病状态下紊乱或丢失的重要分化过程。全身性炎症反应综合征，简称SIRS，是各种临床疾病的灾难性后遗症，包括感染、胰腺炎和体外循环，每年在美国夺去4万多人的生命。与该综合征相关的极高死亡率部分是由于SIRS患者亚群发展为高致死性多系统器官衰竭综合征（MOF）。器官系统的顺序衰竭显然与初始损伤部位无关，但与脓毒症中观察到的血浆细胞因子水平改变有关。在该II期提案中积累的数据将开发一种微型细胞装置，该装置将通过体外导管系统访问。这种体外装置被命名为生物人工肾上皮细胞系统（BRECS），将在感染性休克的临床前大型动物模型中开发和测试治疗SIRS和败血症的有效性。在II期结束时，开发的临床前数据将用于IND申请，用于该治疗性细胞装置治疗感染性休克和SIRS的临床测试。相关性：本提案的目标是开发一种基于细胞的治疗方法，可用于逆转与脓毒性休克患者相关的严重临床事件。该项目的成功将降低感染性休克的极高死亡率，从而有助于患者从这一毁灭性疾病中康复。本提案的长期目标是开发一种生物人工肾上皮细胞系统（BRECS），有效地增加各种疾病过程的治疗价值。目标应用是治疗全身性炎症反应综合征（SIRS）和败血症。美国每年有20万例SIRS患者发生严重脓毒症，即使使用重症监护病房和广谱抗生素，死亡率仍为30.40%。该装置将大大减少脓毒症和SIRS的多器官影响，从而改善受这些疾病过程影响的患者的临床预后。

DESCRIPTION (provided by applicant): Tissue engineering and cell therapy is 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. 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 data accrued in this Phase II proposal will develop a miniature cellular device which will be accessed via an extracorporeal catheter system. This extracorporeal device, named bioartificial renal epithelial cell system (BRECS), will be developed and tested for efficacy in treating SIRS and sepsis in a pre-clinical large animal model of septic shock. 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 and SIRS. 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. PUBLIC HEALTH RELEVANCE The long-term goal of this proposal is to develop a bioartificial renal epithelial cell system (BRECS) that effectively adds therapeutic value to a variety of disease processes. The target application is in the treatment of Systemic Inflammatory Response Syndrome (SIRS) and sepsis. Severe sepsis with SIRS occurs in 200,000 patients annually in the U.S. and has a mortality rate of 30 40%, even with use of intensive care units and broad spectrum antibiotics. This device would greatly reduce the multiorgan effects of sepsis and SIRS, thus improving the clinical outcome of patients affected by these disease processes.