A High Performance Point-of-Care Device for Umbilical Cord Blood Processing

用于脐带血处理的高性能护理点设备

• 批准号: 8253273
• 负责人: Lotien Richard Huang
• 金额: $ 15万
• 依托单位: CYTOVERA, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8253273
• 关键词: Adult; Benchmarking; Blood; Blood Banks; Blood Circulation; Body Weight; Bone Marrow; Bone Marrow Diseases; CD34 gene; Cell Count; Cell Separation; Cell Survival; Cells; Centrifugation; Child; Childhood Leukemia; Childhood Lymphoma; Clinical; Colony-Forming Units Assay; Devices; Disease; Effectiveness; Engineering; Flow Cytometry; Immune; Lead; Left; Life; Methods; Microfluidic Microchips; Outcome; Patients; Performance; Peripheral Blood Stem Cell; Phase; Phenotype; Physiological; Process; Recovery; Safety; Shipping; Ships; Source; Stem cell transplant; Stem cells; System; Time; Transplantation; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; base; dosage; improved; in vitro Assay; in vivo; leukemia/lymphoma; mouse model; novel; point of care; progenitor; prototype; standard care; stem cell therapy

DESCRIPTION (provided by applicant): This project aims to develop a novel microfluidic device that preserves the maximal viability and potency of cord blood stem cells, in order to render cord blood transplantation effective for adult patients with leukemia, lymphoma, and other serious blood and bone marrow diseases. Currently cord blood transplantation yields good outcomes in children (50% - 70% one year survival), and has been shown to have significant advantages over other types of stem cell transplantation. However, cord blood transplantation in adults suffers poor outcomes (~20% one year survival). It is estimated that the dosage of potent stem cells has to be increased by a factor of 3 for adult cord blood transplantation to yield satisfactory outcomes, due to the larger body weights of adult patients. Studies have shown that the current cord blood processing and banking practices lead to as much as ~90% loss in cell potency, particularly during the shipping delay (36 to 48 hrs) and the centrifugal volume reduction step, leaving only 10 - 20% of the original cell potency by the time a unit arrives at a processing facility. The new device proposed here will enable immediate processing of cord blood at point of care, thereby eliminating the loss in viability and potency. The device will be based on a hydrodynamic effect observed in natural blood circulation to allow for gentle and physiological separation of cells. Early prototypes have achieved better initial results than conventional methods: >90% total nucleated cells were recovered with no detectable loss in cell viability (n = 6). Phase I of this project aims to demonstrate the high viability and potency of th cord blood stem cells enriched using an improved prototype device. Phase II aims to optimize the prototype device, validate its safety and effectiveness, and benchmark its performance against standard centrifugation-based systems. Potential impacts of the device include enabling cord blood to replace bone marrow as the primary source of stem cells for transplantation, delivering significantly better patient outcomes, and making cord blood banking and stem cell therapies much more effective. PUBLIC HEALTH RELEVANCE: This project aims to develop a novel device that preserves the maximal viability and potency of cord blood stem cells, in order to render cord blood transplantation effective for adult patients. The proposed device will potentially enable cord blood to replace bone marrow and peripheral blood stem cells as the standard source of stem cells, providing significantly better outcomes and long term survival to patients with leukemia, lymphoma, and many other serious diseases.

描述（由申请人提供）：该项目旨在开发一种新型微流体装置，保留脐带血干细胞的最大活力和效力，以使脐带血移植对患有白血病、淋巴瘤和其他严重血液和骨髓疾病的成年患者有效。目前，脐带血移植在儿童中取得了良好的效果（一年生存率为 50% - 70%），并且已被证明比其他类型的干细胞移植具有显着优势。然而，成人脐带血移植的结果很差（一年存活率约为 20%）。据估计，由于成年患者体重较大，成人脐带血移植的强效干细胞剂量必须增加 3 倍才能获得满意的结果。研究表明，当前的脐带血处理和储存实践导致细胞效力损失高达约 90%，特别是在运输延迟（36 至 48 小时）和离心减容步骤期间，当一个单位到达处理设施时，仅留下原始细胞效力的 10 - 20%。这里提出的新设备将能够在护理点立即处理脐带血，从而消除活力和效力的损失。该装置将基于在自然血液循环中观察到的流体动力学效应，以实现细胞的温和和生理分离。早期原型已取得比传统方法更好的初步结果：回收了 >90% 的总有核细胞，且未检测到细胞活力损失 (n = 6)。该项目的第一阶段旨在证明使用改进的原型设备富集脐带血干细胞的高活力和效力。第二阶段旨在优化原型设备，验证其安全性和有效性，并根据标准离心系统对其性能进行基准测试。该设备的潜在影响包括使脐带血取代骨髓作为移植干细胞的主要来源，显着改善患者的治疗效果，并使脐带血库和干细胞疗法更加有效。 公共健康相关性：该项目旨在开发一种新型装置，可保留脐带血干细胞的最大活力和效力，以使脐带血移植对成年患者有效。拟议的设备将有可能使脐带血取代骨髓和外周血干细胞作为干细胞的标准来源，为患有白血病、淋巴瘤和许多其他严重疾病的患者提供明显更好的结果和长期生存。