Cell Graft Engineering Using Microfluids

使用微流体的细胞移植工程

• 批准号: 7029804
• 负责人: ALLISON HUBEL
• 金额: $ 21.15万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7029804
• 关键词: microfluidics

DESCRIPTION (provided by applicant): The objective of this investigation is to demonstrate proof-of-principal for a microfluidic device capable of removing dimethylsulfoxide from a cryopreserved cell suspension. Hematopoietic cells grafts (both stem cells and mature cells) have become the standard of care for a wide range of hematologic diseases. Traditional methods of stem cell cryopreservation use dimethylsulfoxide (DMSO) as a cryoprotective agent and cell grafts are routinely thawed at the patient bedside and infused directly. The clinical toxicity resulting from the infusion of DMSO into humans is well documented. Removal of DMSO using centrifugation or automated cell washers typically results in a 25-30% cell loss. Therein lies the conundrum: direct infusion of cryopreserved hematopoietic stem cells results in significant adverse reactions but washing cells to remove DMSO results in significant cell losses that, in turn, adversely affect transplant outcome. We propose a new paradigm for processing of post-thaw cell suspensions: the use of microfluidic devices. We hypothesize that microfluidic devices can be used to wash such suspensions effectively while minimizing cell losses. Liquid flows through microscale devices are characterized by low velocity, laminar flow. The cross sectional areas of the devices are small enough that the length scale can approach the diameter of blood cells (~10 micron). The laminar nature of microfluidic flow will permit diffusion-based extraction without the use of a membrane to separate fluid streams. These characteristics, combined with the possibility of fabricating massively- parallel microfluidic systems, therefore, provide an important platform from which to evaluate processing of cells in concentrations and volumes used clinically. This project also represents an important opportunity to translate our understanding of both stem cell biology and microfludics into an application that can directly benefit human health. Reducing cell losses during processing will also increase the access of stem cell based therapies (in particular cord blood stem cells) to more people.

描述（由申请人提供）：这项研究的目的是证明能够从冷冻保存的细胞悬浮液中去除二甲基硫氧化物的微流体设备的原理证明。造血细胞移植（干细胞和成熟细胞）已成为多种血液疾病的护理标准。干细胞冷冻保存的传统方法使用二甲基硫氧化物（DMSO）作为冷冻保护剂和细胞移植物通常在病人的床边解冻并直接注入。充分记录了DMSO输注到人类的临床毒性。使用离心或自动细胞垫圈去除DMSO通常会导致25-30％的细胞损失。其中的难题是：直接输注冷冻保存的造血干细胞会导致严重的不良反应，但洗涤细胞以去除DMSO会导致明显的细胞损失，从而对移植结果产生不利影响。我们提出了一种用于处理后透明细胞悬浮液的新范式：使用微流体设备。我们假设微流体设备可用于有效洗涤此类悬浮液，同时最大程度地减少细胞损失。液体流经微观设备的特征是低速，层流流。设备的横截面面积足够小，长度尺度可以接近血细胞直径（〜10微米）。微流体流的层流性质将允许基于扩散的提取，而无需使用膜分离流体流。因此，这些特征结合了制造大量平行微流体系统的可能性，提供了一个重要的平台，可以从临床上使用浓度和体积来评估细胞的处理。该项目还代表了将我们对干细胞生物学和微塑料的理解转化为可以直接受益于人类健康的应用的重要机会。减少加工过程中的细胞损失还将增加基于干细胞的疗法（尤其是脐带血干细胞）对更多人的访问。