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

描述(申请人提供)：该项目旨在开发一种新型的微流控设备，以保持脐带血干细胞的最大活性和效力，以便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人患者有效。目前，脐带血移植在儿童中取得了良好的效果(一年存活率为50%-70%)，并已被证明比其他类型的干细胞移植具有显著的优势。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，由于成人患者的体重较大，成人脐血移植的有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，目前的脐带血加工和储存做法导致高达90%的细胞效力损失，特别是在运输延迟(36至48小时)和离心量减少步骤期间，当设备到达加工设施时，仅保留原始细胞效力的10%至20%。这里提出的新设备将能够在护理点立即处理脐带血，从而消除活性和效力的损失。该设备将基于在自然血液循环中观察到的流体动力学效应，以允许温和和生理地分离细胞。早期的原型已经取得了比传统方法更好的初步结果：有核细胞总数的90%被回收，细胞活力没有明显的损失(n=6)。该项目的第一阶段旨在展示使用改进的原型装置浓缩的TH脐带血干细胞的高活性和潜能。第二阶段旨在优化原型设备，验证其安全性和有效性，并将其性能与标准的基于离心机的系统进行基准比较。该设备的潜在影响包括使脐带血能够取代骨髓成为移植干细胞的主要来源，提供明显更好的患者结果，并使脐带血库和干细胞治疗更加有效。 公共卫生意义：该项目旨在开发一种新的设备，以保持脐带血干细胞的最大活性和潜力，以便使脐带血移植对成人患者有效。拟议中的设备将有可能使脐带血取代骨髓和外周血干细胞成为干细胞的标准来源，为白血病、淋巴瘤和许多其他严重疾病的患者提供显著更好的结果和长期存活。

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.