Organ banking for transplant—kidney cryopreservation by vitrification and novel nanowarming technology
通过玻璃化和新型纳米加温技术进行移植肾冷冻保存的器官库
基本信息
- 批准号:9912760
- 负责人:
- 金额:$ 58.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-13 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelArteriesBiocompatible MaterialsBlood VesselsCell SurvivalCell physiologyCellular StructuresClinicalConvectionCost SavingsCouplingCryopreservationCryoprotective AgentsCrystal FormationCrystallizationDataDegenerative DisorderDehydrationDevelopmentDialysis procedureElectromagneticsEnsureFamily suidaeFreezingFrequenciesGlassGoalsHealth Care CostsHeartHeart ValvesHeatingHumanIceKidneyKidney TransplantationLifeLife ExpectancyLinkLiquid substanceMagnetic nanoparticlesMagnetismMethodsModelingNitrogenOrganOrgan SizeOrgan TransplantationOryctolagus cuniculusOutcomePatientsPerfusionPolyethylene GlycolsPreparationPreventionProcessPropertyQuality of lifeRewarmingRiskSample SizeSamplingSavingsSilicon DioxideSpeedStabilizing AgentsStructureSystemTechniquesTechnologyTemperatureTestingTimeTissue EngineeringTissue ViabilityTissuesTranslationsTransplantationWorkattenuationbiomaterial compatibilitybiophysical propertiesclinical translationcold temperaturecryogenicsimprovedin vivointerestiron oxide nanoparticlekidney preservationkidney vascular structuremagnetic fieldnanoparticlenanoparticle deliverynanowarmingnew technologynovelpreservationpreventprogramsradio frequencyscale upthermal stresstransplant modelvitreous state
项目摘要
ABSTRACT:
Organ banking has the potential to revolutionize the way organs are used for transplantation. Rewarming
organs such as kidneys from the vitrified state is a critical step in obtaining successful cryopreservation. This
would allow improved allocation, transport, and recipient preparation prior to transplant, while simultaneously
providing a missing link in the potential supply chain for other engineered tissues. Typical freezing processes
cause significant damage to biomaterials through ice crystal formation and cellular dehydration. However, with
the aid of cryoprotectant (CPA) solutions, biospecimens can be stabilized in the vitreous (i.e. “glass” or
“amorphous”) or ice free state, allowing for long-term cryopreservation. Our collaborator and consultant Dr.
Greg Fahy has been able to vitrify rabbit kidneys since the 1980s. However, successful rewarming of these
vitrified kidneys has remained a challenge to translation of vitirification for organ banking. Specifically,
achieving critical warming rates (tens to hundreds of oC/min) necessary to avoid devitirification (i.e.
crystallization) during warming has not been possible. In addition, achieving these rates in a sufficiently uniform
fashion throughout the organ is also required to avoid thermal stresses that can crack the brittle material, and
so both speed and uniformity of warming are of critical importance.
Here we propose to investigate the ability of radiofrequency heated magnetic nanoparticles, or
“nanowarming,” to overcome this major limitation hindering further development of bulk cryopreservation of
kidneys. Although electromagnetic rewarming has been tried, the direct coupling of the waves to tissue will
inherently result in non-uniformity in heating, which leads to crystallization, cracking and differential viability. At
lower radiofrequencies (RF < 1 MHz) alternating magnetic fields (AMFs) can uniformly penetrate tissues
without attenuation and negligible dielectric coupling. Although these lower frequency fields will be unable to
rapidly heat the tissue on their own, they are able to produce significant heating through coupling with
magnetic (e.g. iron-oxide) nanoparticles. We have already demonstrated that this approach can generate
heating rates rapid enough to avoid devitirification in most CPAs of interest (up to 200 oC/min) and should
scale independent of sample size.
The objective of this study is to refine this novel nanowarming technology for use in cryopreserving kidneys
for transplant. To this end, in Aim 1 we will physically characterize CPA and nanoparticle mixtures to heat
rabbit and larger mammalian kidneys. In Aim 2 we will demonstrate our ability to perfuse this CPA and
nanoparticle combination into rabbit kidneys, vitrify and nanowarm while maintaining viability, cellular function
and structural tissue integrity. Finally, in Aim 3 we will demonstate in vivo function after vitrification and
nanowarming by transplant in rabbits and scaling for use in human kidneys
In summary, the focus of this proposal will be to leverage our breakthrough nanowarming technology by
optimizing CPA composition and nanoparticle delivery in rabbit kidneys with proof of principle work to scale up
to porcine and human kidneys for eventual clinical kidney banking and transplantation.
摘要:
器官库有可能彻底改变器官用于移植的方式。复温
从玻璃化状态获得器官如肾脏是获得成功冷冻保存的关键步骤。这
将允许在移植前改进分配、运输和受体准备,同时
为其他工程组织的潜在供应链提供缺失的环节。典型的冷冻过程
通过冰晶形成和细胞脱水对生物材料造成显著损害。但随着
在冷冻保护剂(CPA)溶液的帮助下,生物样本可以稳定在玻璃体(即“玻璃”或“透明”)中。
“无定形”)或无冰状态,允许长期冷冻保存。我们的合作者和顾问博士。
格雷格·法希自20世纪80年代以来一直能够玻璃化兔子肾脏。然而,成功的复温,
玻璃化肾脏仍然是将玻璃化转化为器官库的挑战。具体地说,
达到避免偏差所需的临界升温速率(数十至数百oC/min)(即
在加热期间结晶)是不可能的。此外,以足够均匀的方式实现这些速率,
还需要整个器官的时尚,以避免可能使脆性材料破裂的热应力,
所以升温的速度和均匀性都至关重要。
在这里,我们建议研究射频加热的磁性纳米粒子的能力,或
“冷冻保存”,以克服这一主要限制,阻碍进一步发展的散装冷冻保存的
肾脏尽管已经尝试了电磁复温,但是波与组织的直接耦合将导致
固有地导致加热不均匀性,这导致结晶、开裂和不同的活性。在
低射频(RF < 1 MHz)交变磁场(AMF)可以均匀地穿透组织
而没有衰减和可忽略的介电耦合。虽然这些低频场将无法
快速加热组织本身,他们能够产生显着的加热通过耦合与
磁性(例如氧化铁)纳米颗粒。我们已经证明,这种方法可以产生
加热速率足够快,以避免大多数相关CPA中的偏差(高达200 oC/min),并且应
规模独立于样本量。
本研究的目的是改进这种新的冷冻技术用于冷冻保存肾脏
进行移植为此,在目标1中,我们将对CPA和纳米颗粒混合物进行物理表征,
兔子和大型哺乳动物的肾脏。在目标2中,我们将展示我们灌注该CPA的能力,
将纳米颗粒组合物植入兔肾中,玻璃化和冷冻,同时保持活力、细胞功能
和结构组织完整性。最后,在目标3中,我们将证明玻璃化冷冻后的体内功能,
兔肾移植和人肾刮除
总之,本提案的重点将是利用我们突破性的自动化技术,
优化CPA组合物和兔肾中的纳米颗粒递送,并证明原理工作以扩大规模
猪和人的肾脏用于最终的临床肾脏储存和移植。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN C BISCHOF其他文献
JOHN C BISCHOF的其他文献
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{{ truncateString('JOHN C BISCHOF', 18)}}的其他基金
Resources for Drosophila embryo cryopreservation at lab and stock center scale
实验室和库存中心规模的果蝇胚胎冷冻保存资源
- 批准号:
10569277 - 财政年份:2023
- 资助金额:
$ 58.45万 - 项目类别:
Cryopreservation and nanowarming enables whole liver banking for transplantation, cell therapy and biomedical research
冷冻保存和纳米加温使整个肝脏库能够用于移植、细胞治疗和生物医学研究
- 批准号:
10584878 - 财政年份:2023
- 资助金额:
$ 58.45万 - 项目类别:
Subzero preservation of vascular composite allografts
同种异体复合血管的低温保存
- 批准号:
10664308 - 财政年份:2022
- 资助金额:
$ 58.45万 - 项目类别:
Engineering optimization and scaling enables high quality pancreatic islet cryopreservation for banking and transplant
工程优化和扩展可实现高质量胰岛冷冻保存以用于储存和移植
- 批准号:
10680579 - 财政年份:2021
- 资助金额:
$ 58.45万 - 项目类别:
Engineering optimization and scaling enables high quality pancreatic islet cryopreservation for banking and transplant
工程优化和扩展可实现高质量胰岛冷冻保存以用于储存和移植
- 批准号:
10343955 - 财政年份:2021
- 资助金额:
$ 58.45万 - 项目类别:
Organ banking for transplant--kidney cryopreservation by vitrification and novel nanowarming technology
移植器官库——玻璃化肾脏冷冻保存和新型纳米加温技术
- 批准号:
10657291 - 财政年份:2018
- 资助金额:
$ 58.45万 - 项目类别:
Breakthrough Tissue and Organ Preservation and Transplantation Using Scaled-Up Nanowarming Technology
利用大规模纳米变暖技术实现突破性组织和器官保存和移植
- 批准号:
9980462 - 财政年份:2017
- 资助金额:
$ 58.45万 - 项目类别:
Breakthrough Tissue and Organ Preservation and Transplantation Using Scaled-Up Nanowarming Technology
利用大规模纳米变暖技术实现突破性组织和器官保存和移植
- 批准号:
9757813 - 财政年份:2017
- 资助金额:
$ 58.45万 - 项目类别:
Gold nanoparticle laser warming of cryopreserved zebrafish embryos
金纳米颗粒激光对冷冻斑马鱼胚胎的加温
- 批准号:
10016844 - 财政年份:2017
- 资助金额:
$ 58.45万 - 项目类别:
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