AUTOMATED CLOSED SYSTEM FOR DMSO REMOVAL FROM PERIPHERAL BLOOD STEM CELLS

用于从外周血干细胞中去除 DMSO 的自动封闭系统

• 批准号: 7494589
• 负责人: ERIK J. WOODS
• 金额: $ 48.52万
• 依托单位: GENERAL BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494589
• 关键词: Abdominal Cramps; Acute Kidney Failure; Adverse event; Adverse reactions; Autologous; Back; Blood; Blood Platelets; Blood and Blood Products; CD34 gene; Cardiac; Cardiovascular system; Cell Count; Cell Transplants; Cells; Centrifugation; Class; Clinical; Clinical Research; Collecting Cell; Cryopreservation; Cyclic GMP; Development; Devices; Diarrhea; Diffusion; Dimethyl Sulfoxide; Disease; Dyspnea; Effectiveness; Engraftment; Ensure; Equipment; Event; Excision; Exposure to; Fever; Flow Cytometry; Flushing; Freezing; Future; Goals; Headache; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Hemolysis; High Dose Chemotherapy; Hospitalization; Hospitals; Hour; Human; In Vitro; Infusion procedures; Institution; International; Ischemia; Laboratories; Lead; Lung; Malignant neoplasm of testis; Marketing; Marrow; Measures; Mechanics; Medical Device; Methods; Morbidity - disease rate; Multiple Myeloma; Nausea; Nausea and Vomiting; Nervous System Trauma; Neuroblastoma; Neurologic; Operative Surgical Procedures; Outcome; Patients; Peripheral Blood Stem Cell; Phase; Preclinical Testing; Procedures; Process; Public Health; Range; Recovery; Recovery of Function; Reporting; Research; SCID Mice; Safety; Sales; Sampling; Skin; Standards of Weights and Measures; Stem cell transplant; Sterility; Stress; Symptoms; System; Techniques; Testing; Time; Transplant Recipients; Transplantation; Umbilical Cord Blood; United States Food and Drug Administration; Work; austin; cerebrovascular; cost; design; engineering design; follow-up; improved; in vivo; innovation; international center; leukemia/lymphoma; malignant breast neoplasm; mouse model; peripheral blood; pre-clinical; prevent; prototype; research clinical testing

DESCRIPTION (provided by applicant): High dose chemotherapy followed by peripheral blood hematopoietic stem cell (PBSC) transplantation is frequently used for treating various hematologic malignancies. To facilitate this process, autologous PBSC are typically collected, cryopreserved and stored for some period of time. Current PBSC cryopreservation requires the use of molar concentrations of the cryoprotectant additive dimethyl sulfoxide (DMSO). Typically, frozen-thawed cells are transplanted back into patients along with DMSO. However, reinfusion of DMSO has long been associated with various adverse events, ranging from skin flushing, headache, fever, dyspnea, abdominal cramping, nausea, and diarrhea to more sever effects such as, hemolysis, cardiovascular symptoms and cerebrovascular ischemia leading to neurological events. These can result in increased morbidity, prolonged hospitalization, and increased treatment-related costs. Currently, when removal of DMSO is attempted, the procedures typically involve cell "washing" using centrifugation. These methods introduce mechanical forces and osmotic stress causing cell packing/clumping and potential significant cell loss. They also require additional laboratory staff as well, and take between 3 and 4 hours of work per patient, which makes the procedure more expensive and practically difficult for many institutions. Finally, it is difficult to kept the cells in a "closed" system during cell washing, which may lead to contamination. It is the goal of this proposal to finalize, build under appropriate design control and test the automated, portable, closed-system diffusion-driven washing device developed in Phase I for use in clearance of DMSO from PBSC, to prevent infusion of DMSO into patients during clinical transplant without loss of cell numbers or cell functionality. In this Phase II research, the device will be evaluated in preclinical and ultimately clinical testing for 510(k) premarket application to the FDA for clearance to market the device in Phase III. Preclinical testing will rely on in vitro flow cytometry and clonogenic ability as well as engraftment in a NOD/SCID mouse model. Clinical testing will include use in up to 20 multiple myeloma patients, pending acceptable preclinical results. PUBLIC HEALTH RELEVANCE STATEMENT Peripheral blood stem cell transplant (PBSC) is used to treat many types of diseases, such as lymphoma, leukemia, multiple myeloma, breast cancer, testicular cancer, neuroblastoma and others. These cells are collected, frozen and stored over several periods to ensure enough are available for transplant, and to freeze these cells a compound called dimethyl sulfoxide (DMSO) is added. This DMSO protects the cells during freezing, but can be damaging to cells after they are thawed and can cause complications with transplantation of PBSC. The goal of this research is to produce a device to easily remove DMSO from PBSC before they are transplanted, increasing effectiveness of the cells and reducing potential complications.

描述（由申请人提供）：高剂量化疗后进行外周血造血干细胞（PBSC）移植常用于治疗各种血液恶性肿瘤。为了促进这一过程，通常收集自体PBSC，冷冻保存并储存一段时间。目前的PBSC冷冻保存需要使用摩尔浓度的冷冻保护剂添加剂二甲基亚砜（DMSO）。通常，将冷冻-解冻的细胞与DMSO一起沿着移植回患者体内。然而，DMSO的再输注长期以来与各种不良事件相关，从皮肤潮红、头痛、发热、呼吸困难、腹部绞痛、恶心和腹泻到更严重的影响，如溶血、心血管症状和脑血管缺血，导致神经系统事件。这些可能导致发病率增加、住院时间延长和治疗相关费用增加。目前，当尝试去除DMSO时，该程序通常涉及使用离心的细胞“洗涤”。这些方法引入机械力和渗透应力，导致细胞堆积/结块和潜在的显著细胞损失。它们还需要额外的实验室工作人员，并且每个病人需要3到4个小时的工作，这使得该程序对许多机构来说更加昂贵和实际困难。最后，在细胞洗涤期间难以将细胞保持在“封闭”系统中，这可能导致污染。本提案的目标是最终确定、在适当的设计控制下构建并测试I期开发的用于从PBSC中清除DMSO的自动化、便携式、封闭系统扩散驱动清洗装置，以防止在临床移植期间向患者输注DMSO，而不会损失细胞数量或细胞功能。在这项II期研究中，将在临床前和最终临床试验中对该器械进行评价，以便向FDA提交510（k）上市前申请，以获得III期器械上市许可。临床前试验将依赖于体外流式细胞术和克隆形成能力以及NOD/SCID小鼠模型中的植入。临床试验将包括在多达20例多发性骨髓瘤患者中使用，等待可接受的临床前结果。外周血干细胞移植（PBSC）是一种治疗多种疾病的有效方法，包括淋巴瘤、白血病、多发性骨髓瘤、乳腺癌、睾丸癌、神经母细胞瘤等。这些细胞被收集，冷冻和储存几个时期，以确保有足够的可用于移植，并冷冻这些细胞，一种称为二甲基亚砜（DMSO）的化合物被添加。这种DMSO在冷冻过程中保护细胞，但在解冻后可能对细胞造成损害，并可能导致PBSC移植并发症。这项研究的目标是生产一种装置，可以在移植PBSC之前轻松去除其中的DMSO，提高细胞的有效性并减少潜在的并发症。