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: 7054977
• 负责人: ERIK J. WOODS
• 金额: $ 13.37万
• 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 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054977
• 关键词: bioengineering /biomedical engineering; biomedical equipment; biomedical equipment development; biotechnology; cell bank /registry; clinical research; dimethylsulfoxide; hematopoietic stem cells; human tissue; laboratory mouse; stem cell transplantation; tissue /organ preservation

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 keep the cells in a "closed" system during cell washing, which may lead to contamination. It is the goal of this proposal to refine and optimize an automated, portable, closed-system diffusion-driven washing device 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 I research, the device will be optimized for effective clearance of DMSO from cell suspension solutions while allowing high cell recovery with maintenance of cell functional viability as assessed by in vitro clonogenic ability as well as engraftment in a NOD/SCID mouse model.

描述（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，通常会收集自体 PBSC、冷冻保存并储存一段时间。目前的 PBSC 冷冻保存需要使用一定摩尔浓度的冷冻保护剂添加剂二甲亚砜 (DMSO)。通常，冻融的细胞与 DMSO 一起移植回患者体内。然而，长期以来，回输 DMSO 一直与各种不良事件相关，从皮肤潮红、头痛、发烧、呼吸困难、腹部绞痛、恶心和腹泻到更严重的影响，如溶血、心血管症状和导致神经系统事件的脑血管缺血。这些可能导致发病率增加、住院时间延长以及治疗相关费用增加。目前，当尝试去除 DMSO 时，程序通常涉及使用离心“洗涤”细胞。这些方法引入机械力和渗透应力，导致细胞堆积/聚集和潜在的显着细胞损失。它们还需要额外的实验室工作人员，每个患者需要花费 3 到 4 个小时的工作时间，这使得该过程对于许多机构来说更加昂贵且实际上更加困难。最后，在细胞洗涤过程中很难将细胞保持在“封闭”系统中，这可能导致污染。该提案的目标是完善和优化一种自动化、便携式、封闭系统扩散驱动清洗装置，用于从 PBSC 中清除 DMSO，以防止在临床移植过程中将 DMSO 输注到患者体内，而不会损失细胞数量或细胞功能。在此一期研究中，该设备将进行优化，以有效清除细胞悬浮液中的 DMSO，同时允许高细胞回收率并维持细胞功能活力（通过体外克隆形成能力以及 NOD/SCID 小鼠模型中的植入来评估）。