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

• 批准号: 10383717
• 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
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383717
• 关键词: Address; Alcohols; Alkanes; Anaerobic Bacteria; Animals; Antioxidants; Biochemical; Blood; Blood Banks; Cells; Classification; Clinical; Communities; Cryopreservation; Development; Erythrocyte Transfusion; Erythrocytes; Ethics; Food; Goals; Gold; 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; Savings; Series; Shapes; Shipping; Site; Solid; Surface; Temperature; Time; Tissue Engineering; Tissues; Transfusion; Uncertainty; Validation; Water; Whole Blood; Work; World War I; aged; alkalinity; aqueous; base; cell injury; cell type; clinically significant; cold temperature; expectation; experience; experimental study; improved; in vivo; milliliter; novel; preservation; protein expression; seal; success; wasting

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) 可能是输注最多的血液成分和储存最广泛的细胞 类型。虽然红细胞的冷藏 (+4 oC) 在过去几十年中已经通过标准得到了极大的改善 在临床环境中的储存时间为 42 天，最近的临床回顾以及实验室研究表明 超过 14 天的储存红细胞可能具有截然不同的生化特性，并且可能劣质 患者的结果。在这里，我们建议根据我们最近的研究开发一种红细胞保存方法 在水溶液深度过冷（DSC）方面取得突破，我们可以实现看似稳定的结果 在极低温度（低至 -20 oC）下长时间进行大容量过冷。这是 通过与水不混溶的烃基液体对水溶液进行表面密封来实现。我们的中央 基于初步研究和先前工作的假设是红细胞 DSC 可以立即提供 实用、高品质、可长期保存，可替代目前临床冷藏标准。我们的 方法是首先为存储相关伤害建立一个稳健的表征框架，以便 a) 建立 红细胞 DSC 的基本温度优化，b) 同时将该基本方法的细胞质量与 冷藏和冷冻保存。然后，我们将根据我们的经验补充 DSC 方法 减轻脂质过氧化、氧化应激、膜损伤和代谢抑制 红细胞保存的最新进展，例如厌氧保存以实现红细胞的长期保存 体积小。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）并行。我们的最终目标是使用这些强大的存储 DSC 策略将临床单位（~300 ml）红细胞保存 150 天。通过完成这个项目，我们期望， 展示一种新方法，可将红细胞的储存时间显着延长至 150 天，从而减轻 当前方法的问题。长远来看“大体积DSC”方法，广泛适用于所有细胞， 组织和器官；尤其是那些不适合冷冻保存的。这些进步将积极 通过存储生命物质以用于细胞/器官移植、工程化应用来影响医疗保健 组织物流和食品储存等