Subzero Non-freezing preservation of whole mammalian organisms

整个哺乳动物有机体的零下非冷冻保存

• 批准号: 10705577
• 负责人: Korkut Uygun
• 金额: $ 21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705577
• 关键词: Air; Alkanes; Applications Grants; Area; Birth; Brain; Breathing; Carbohydrates; Caring; Cells; Data; Diapause; Endothelium; Environment; Extracorporeal Membrane Oxygenation; Formulation; Freezing; Funding Mechanisms; Goals; Grant; Heart; Hemoglobin; Hibernation; Histologic; Hour; Human; Ice; Immersion; Individual; Injury; Intestines; Ischemia; Kidney; Liquid substance; Literature; Liver; Lung; Mammals; Medicine; Metabolic; Methods; Mission; Modeling; Molecular; Monitor; Mucous body substance; Mus; Muscle; National Institute of General Medical Sciences; Nature; Neonatal; Oils; Operative Surgical Procedures; Organ; Organism; Oxygen; Pathway interactions; Perfusion; Phase Transition; Phenotype; Physiological; Planet Mars; Probability; Protocols documentation; Race; Rattus; Recovery; Research; Research Project Grants; Resuscitation; Rewarming; Risk; Saline; Site; Skin; Societies; Suspensions; Techniques; Technology; Temperature; Testing; Thermodynamics; Thigh structure; Time; Tissues; Trauma; Variant; Vial device; Water; Whole Organism; animation; body cavity; crosslink; design; feasibility testing; gastrointestinal; inhibitor; innovation; interest; mouse model; natural hypothermia; neonatal mice; neonate; new technology; novel; postnatal; preservation; programs; public health relevance; sealant; success; technology development

ABSTRACT Realizing suspended animation for humans would be transformative for the society: in long term applications where months of preservation is needed, it would enable planetary missions to Mars and beyond. In the more immediate uses it could be enabling for delayed resuscitation purposes in certain cases. Extended suspended animation is commonly observed in nature including several mammalian species which hibernate at subzero environments with ambient temperature as low as -30 ºC. While such high subzero temperatures (defined here as 0 ºC to -30 ºC) is utilized commonly by nature as a means to establish whole organism preservation for extended durations, subzero non-freezing preservation has not been explored for mammalians in literature (see Significance) and remain a profitable area for research. Our overarching goal is to push the boundaries of scientific discovery by enabling metabolic stasis and reanimation for an organism without the natural capacity for suspended animation. The objective of this NIGMS exploratory research grant for technology development is to test the viability of sub-zero, non-freezing (SZNF) storage of a mammal for the first time in literature. The studies would also lead to preliminary data in a context where none exists, which in turn would enable continuation with a more traditional funding mechanism once the risks are reduced and mechanistic targets are identified to enable hypothesis driven research. This objective was formulated based on our team's prior success in scaling subzero nonfreezing preservation to human livers, which provided us with key new technologies enabling control of intracellular carbohydrate levels, understanding of endothelial sensitivity to ischemia and strategies for mitigation, and machine-assisted recovery/reanimation techniques to ameliorate preservation injury. However, the transition from a single organ to an entire mammalian organism presents a vertical step forward, a potential breakthrough but with considerable risk. As such, this technology design-directed proposal specifically matches the program requirements for this exploratory grant mechanism. As a result of these studies, we expect to develop novel technologies that enables preservation of neonatal and post- natal mice in subzero temperatures. To do so, we aim to develop several novel protocols and cryopreservatives to avoid freezing in the context of whole-organism storage. These results are expected to lead to preliminary data that shows survival after days of subzero storage, which will motivate future research, as well as key data that will enable formulation of new hypotheses that will enable the utilization of more traditional funding mechanisms.

抽象的 实现人类假死将对社会产生变革：在长期应用中 需要数月的保存时间，它将能够在更直接的用途中实现前往火星及更远地区的行星任务。 在某些情况下，通常可以实现延迟复苏。 在自然界中观察到，包括几种在零下环境下冬眠的哺乳动物物种 温度低至 -30 ℃，而通常使用如此高的零度以下温度（此处定义为 0 ℃ 至 -30 ℃）。 本质上是一种长期保存整个生物体的手段，低温非冷冻保存 文献中尚未对哺乳动物进行探索（参见意义），并且仍然是一个有利可图的研究领域。 我们的首要目标是通过实现代谢停滞和复活来突破科学发现的界限 对于不具有假死自然能力的生物体，本次 NIGMS 探索性研究的目的。 技术开发补助金旨在测试哺乳动物的零度以下非冷冻（SZNF）储存的可行性 这些研究还将在不存在的背景下得出初步数据，这反过来又会产生影响。 一旦风险降低且机械目标得以实现，就可以继续采用更传统的融资机制 确定这一目标是基于我们团队之前的成功。 将零下非冷冻保存扩展到人类肝脏，这为我们提供了关键的新技术来实现控制 细胞内碳水化合物水平，了解内皮对缺血的敏感性和缓解策略，以及 然而，机器辅助恢复/复活技术可以改善保存损伤。 器官到整个哺乳动物有机体的发展呈现出垂直的进步，这是一个潜在的突破，但具有相当大的意义 因此，这项以技术设计为导向的提案特别符合该探索性的计划要求。 补助金机制。 作为这些研究的结果，我们期望开发出能够保存新生儿和产后新生儿的新技术。 为此，我们的目标是开发几种新的方案和冷冻保存剂来避免。 预计这些结果将产生显示整个生物体冷冻情况的初步数据。 数天的零下储存后的存活率，这将激励未来的研究，以及有助于制定配方的关键数据 新的假设将能够利用更传统的融资机制。