Deep Supercooling of Red Blood Cells: Towards Practical Long Term Storage

红细胞深度过冷：走向实用的长期储存

基本信息

批准号：
10600827
负责人：
Osman Berk USTA
金额：
$ 37.78万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10600827
关键词：
Address Alcohols Alkanes Anemia Animals Antioxidants Biochemical Blood Blood Banks Blood Component Transfusion Cells Classification Clinical Communities Cryopreservation Development Erythrocyte Transfusion Erythrocytes Ethics Food Goals Healthcare Heat shock proteins Hemoglobin Hepatocyte Hospitals Hydrocarbons Ice In Vitro Inferior Injury Laboratory Study Lesion Life Lipid Peroxidation Liquid substance Logistics Medical Membrane Metabolic Metabolism Methods Morphology Oils Organ Organ Transplantation Outcome Oxidative Stress Patients Process Property Randomized, Controlled Trials Recovery Safety Sampling Series Shapes Shipping Site Solid Surface Technology Temperature Time Tissue Engineering Tissues Transfusion Uncertainty Validation Water Whole Blood Work World War I aged aqueous cell injury cell type clinically significant cold temperature expectation experience experimental study improved in vivo milliliter novel preservation protein expression seal success wasting

项目摘要

Abstract Red blood cells (RBCs) are possibly the most transfused blood component and the most widely stored cell type. While cold storage (+4 oC) of RBCs has been vastly improved in the last few decades with a standard storage time of 42 days in clinical settings, recent clinical retrospective as well as laboratory studies indicate that beyond 14 days of storage RBCs might have vastly different biochemical properties and possibly inferior outcomes in patients. Here, we propose to develop an RBC preservation method based on our recent breakthrough in deep supercooling (DSC) of aqueous solutions where we can achieve seemingly stable supercooling for large volumes and at very low temperatures (down to -20 oC) for very long times. This is achieved by surface sealing of aqueous solutions via water-immiscible hydrocarbon-based liquids. Our central hypothesis, based on preliminary studies and prior work, is that DSC of RBCs can provide an immediately practical, high quality, and long-term storage, as an alternative to current clinical standard of cold storage. Our approach is to first establish a robust characterization framework for storage related injuries to a) establish the basic temperature optimization of DSC for RBCs, b) while comparing the cell quality of this basic approach to cold storage and cryopreservation. We will then supplement the DSC approach drawing from our experience in alleviating lipid peroxidation, oxidative stress, and membrane injuries and metabolic suppression along with recent advances in RBC preservation such as anaerobic preservation to achieve long-term storage of RBCs in small volumes. Finally, we aim to extend the range of parameters for DSC to the 150-500 ml range (volume), ~- 25-30 oC (temperature), and 150 days (time) in parallel. Our final goal is to conduct storage with these robust DSC strategies to preserve a clinical unit (~300 ml) of RBCs for 150 days. By completing this project, we expect, to demonstrate a novel method to dramatically extend the storage time for RBCs to 150 days whereby alleviating problems of current approaches. In the long-term the “large volume DSC” method, is widely applicable to all cell, tissue and organs; especially those that are not amenable to cryopreservation. These advances will positively influence healthcare by enabling storage of living matter for applications in cell/organ transplantation, engineered tissue logistics, and food storage among others

抽象的红细胞（RBC）可能是最流血的血液成分，并且储存最广泛的细胞类型。虽然在过去的几十年中，RBC的冷藏（+4 oC）已大大改善在临床环境中的存储时间为42天，最近的临床回顾性以及实验室研究表明超过14天的存储RBC可能具有截然不同的生化特性和可能的劣等患者的结果。在这里，我们建议根据我们的最新水溶液的深层过冷（DSC）的突破，我们可以实现看似稳定的长时间的大量量和非常低的温度（降至-20 oC）过冷。这是通过通过水不混杂的碳氢化合物液体对水溶液的表面密封实现。我们的中心基于初步研究和先前工作的假设是RBC的DSC可以立即提供实用，高质量和长期存储，作为当前冷藏临床标准的替代方案。我们的方法是首先建立一个强大的表征框架，以使其与存储相关的伤害a）建立 RBC的DSC的基本温度优化，b）在比较这种基本方法的细胞质量的同时冷藏和冷冻保存。然后，我们将根据我们的经验来补充DSC方法减轻脂质过氧化，氧化应激，膜损伤和代谢抑制以及 RBC保存的最新进展，例如厌氧保存，以实现RBC的长期存储小卷。最后，我们的目标是将DSC的参数范围扩展到150-500 mL范围（体积），〜- 25-30 OC（温度）和150天（时间）并联。我们的最终目标是用这些强大的 DSC保留临床单位（约300 mL）RBC的策略150天。通过完成该项目，我们希望为了展示一种新颖的方法，可以将RBC的存储时间大幅度扩展到150天，从而减轻当前方法的问题。从长远来看，“大体积DSC”方法广泛适用于所有细胞，组织和器官；特别是那些不适合冷冻保存的人。这些进步将积极通过使生活事项存储用于细胞/器官移植，工程设计来影响医疗保健组织物流和食物存储等