A quantitative viability metric for liver transplantation using Resonance Raman Spectroscopy
使用共振拉曼光谱进行肝移植的定量活力指标
基本信息
- 批准号:10562740
- 负责人:
- 金额:$ 51.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-15 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:AcuteAllograftingAnimalsBiopsyCardiac DeathCellsCessation of lifeChronicClinicalCompensationDataDevicesDiseaseExposure toFamily suidaeFunctional disorderGoalsHeartHumanImprove AccessIndustry CollaborationInjuryInterventionLifeLiverLogistic RegressionsMammalsMeasurementMeasuresMethodologyMethodsMitochondriaModelingOperative Surgical ProceduresOrganOrgan DonationsOrgan DonorOrgan TransplantationOrgan ViabilityOrgan failureOutcomeOxidation-ReductionPatientsPerfusionPlayRaman Spectrum AnalysisRattusRecoveryReperfusion InjuryResearchResearch PersonnelResourcesRiskRodentRodent ModelRoleSamplingScientistSurfaceSurgeonSurvival RateTechnologyTimeTissuesTranslatingTransplantationValidationWaiting ListsWarm IschemiaWorkarmattributable mortalitybody systemconditioningcostend-stage organ failureflexibilityimaging platformindexinginjuredinnovationliver biopsyliver injuryliver transplantationmeetingsnovelorgan allocationorgan injurypost-transplantpreclinical studyresponsesuccesstissue injury
项目摘要
PROJECT SUMMARY
Organ transplantation is a life-saving treatment for end-stage organ disease; however, there is a severe shortage
of donor organs whereby only ~36% of wait-listed patients receive a transplant. At the same time, many vital
organs that may be transplantable are discarded - some estimates suggest that up to 25% of recovered organs are
not ultimately transplanted, and there are additional pools of unrecovered organs that are only marginally
damaged. However, because of their uncertain viability and the high cost of an unsuccessful transplant, none of
these potential organs are used while transplantation of just a fraction could dramatically reduce the organ
shortage.
A particularly large target of untapped donor organs are marginally injured warm ischemic organs from
Donation after Circulatory Death (DCD). While these organs have been correlated to lower survival rates and
increased post-transplant complications, machine perfusion technology holds the promise of reconditioning
some of these organs, thereby dramatically increasing availability. However, a critical bottleneck that impacts
experimental and clinical advances in reconditioning organs are developing non-objective metrics that can
definitively ascertain if an organ is viable prior to transplantation. Clinically, since organ allocation is already
severely restricted by time, these criteria need to be defined for each organ rapidly and preferably in real-time.
Experimentally, access to flexible platforms would increase the scale and number of researchers that can tackle
these difficult problems. In response to this need, we propose to develop a novel imaging platform that will use
Resonance Raman Spectroscopy (RRS) to quantify mitochondrial redox state on tissue surfaces/biopsies and
mitochondrial breakdown products in the perfusate. Our approach is unique in organ transplantation assessment
since: 1) results are obtained in less than 3 minutes and are non-destructive, and 2) offers the flexibility required
for diverse organ systems, significantly increasing the impact of the proposed work.
While we will target diverse transplantable organs, we focus our initial efforts on liver through execution of two
specific aims. We will develop a benchtop RRS device with the capacity to integrate several types of
measurements on livers, including biopsies, surface measurements, and perfusate samples. In Specific Aim 1, we
will apply and validate the biopsy cell and extendable arm that enables liver biopsies and surface measurements
to calculate the ratio of reduced to total mitochondria (defined as Resonance Raman Reduced Mitochondrial
Ratio, 3RMR). In Specific Aim 2, we will apply and validate the perfusate cell that is compatible with the same
benchtop RRS device to quantify mitochondrial breakdown products in real-time from the perfusate (defined as
the Perfusate Viability Index, PVI). In SA1-2, we will define the 3RMR/PVI threshold values that if exceeded
will indicate irreversible liver injury, beginning with rigorous studies in rodents before measuring samples from
discarded human DCD livers during machine perfusion.
项目摘要
器官移植是治疗终末期器官疾病的一种挽救生命的治疗方法;然而,
捐赠器官的数量很少,只有约36%的等待患者接受移植。与此同时,许多重要
可移植的器官被丢弃----一些估计表明,多达25%的回收器官被丢弃。
最终没有移植,还有一些未恢复的器官,
损坏然而,由于其不确定的生存能力和不成功移植的高成本,
这些潜在的器官被使用,而仅仅一小部分的移植就可能大大减少器官的数量。
短缺
一个特别大的未开发的供体器官的目标是轻微损伤的热缺血器官,
循环性死亡后捐献(DCD)。虽然这些器官与较低的存活率有关,
移植后并发症增加,机器灌注技术有望修复
其中一些器官,从而显着增加了可用性。然而,一个关键的瓶颈,
器官修复的实验和临床进展正在开发非客观的指标,
在移植前确定一个器官是否可行。临床上,由于器官分配已经
由于受到时间的严格限制,需要为每个器官迅速地并且最好是实时地确定这些标准。
从实验上看,使用灵活的平台将增加研究人员的规模和数量,
这些难题。为了满足这一需求,我们建议开发一种新型的成像平台,
共振拉曼光谱(RRS),用于量化组织表面/活检组织上的线粒体氧化还原状态,
线粒体的分解产物。我们的方法在器官移植评估中是独一无二的
因为:1)在不到3分钟内获得结果,并且是非破坏性的,2)提供所需的灵活性
为不同的器官系统,大大增加了拟议的工作的影响。
虽然我们将针对不同的可移植器官,但我们将通过执行两个
明确的目标。我们将开发一种台式RRS设备,该设备能够集成多种类型的
对肝脏的测量,包括活组织检查、表面测量和灌注液样本。在具体目标1中,
将应用并验证活检单元和可扩展臂,使肝脏活检和表面测量成为可能
计算还原的线粒体与总线粒体的比率(定义为共振拉曼还原的线粒体
比率,3RMR)。在特定目标2中,我们将应用并验证与相同的灌注液池兼容的灌注液池。
台式RRS装置,以实时定量来自灌注液的线粒体分解产物(定义为
灌注液活力指数PVI)。在SA 1 -2中,我们将定义3RMR/PVI阈值,如果超过该阈值,
将表明不可逆的肝损伤,在测量来自啮齿动物的样本之前,
在机器灌注期间丢弃的人DCD肝脏。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Shannon Noella Tessier其他文献
Shannon Noella Tessier的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Shannon Noella Tessier', 18)}}的其他基金
Cryopreservation of zebrafish larvae and embryos for biomedical research
用于生物医学研究的斑马鱼幼虫和胚胎的冷冻保存
- 批准号:
10626493 - 财政年份:2023
- 资助金额:
$ 51.46万 - 项目类别:
High subzero heart preservation: from zebrafish to mammals
高度零下心脏保存:从斑马鱼到哺乳动物
- 批准号:
10183964 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortage
全心假死:借力斑马鱼解决器官短缺
- 批准号:
10599244 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortage
全心假死:借力斑马鱼解决器官短缺
- 批准号:
10366091 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
High subzero heart preservation: from zebrafish to mammals
高度零下心脏保存:从斑马鱼到哺乳动物
- 批准号:
10370426 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
High subzero heart preservation: from zebrafish to mammals
高度零下心脏保存:从斑马鱼到哺乳动物
- 批准号:
10601049 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortage
全心假死:借力斑马鱼解决器官短缺
- 批准号:
10336180 - 财政年份:2021
- 资助金额:
$ 51.46万 - 项目类别:
Whole heart suspended animation: leveraging the zebrafish to solve the organ shortage
全心假死:借力斑马鱼解决器官短缺
- 批准号:
9902524 - 财政年份:2019
- 资助金额:
$ 51.46万 - 项目类别:
相似海外基金
Establishment of novel osteochondral allografting combined with growth factor- collagen-binding domain fusion technology
新型同种异体骨软骨移植联合生长因子-胶原蛋白结合域融合技术的建立
- 批准号:
26462277 - 财政年份:2014
- 资助金额:
$ 51.46万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Translating PTH Therapy as an Adjuvant for Structural Allografting
将 PTH 疗法转化为结构性同种异体移植的佐剂
- 批准号:
8344380 - 财政年份:2012
- 资助金额:
$ 51.46万 - 项目类别:
Composite Allografting for Promoting Survival of Corneal Transplants
复合同种异体移植促进角膜移植的存活
- 批准号:
7878675 - 财政年份:2009
- 资助金额:
$ 51.46万 - 项目类别:
Composite Allografting for Promoting Survival of Corneal Transplants
复合同种异体移植促进角膜移植的存活
- 批准号:
7677758 - 财政年份:2009
- 资助金额:
$ 51.46万 - 项目类别:
Augmenting Antitumor Immunity after Allografting
增强同种异体移植后的抗肿瘤免疫力
- 批准号:
7466112 - 财政年份:2008
- 资助金额:
$ 51.46万 - 项目类别:
Augmenting Antitumor Immunity after Allografting
增强同种异体移植后的抗肿瘤免疫力
- 批准号:
8010394 - 财政年份:2008
- 资助金额:
$ 51.46万 - 项目类别:
Augmenting Antitumor Immunity after Allografting
增强同种异体移植后的抗肿瘤免疫力
- 批准号:
8208131 - 财政年份:2008
- 资助金额:
$ 51.46万 - 项目类别:
Augmenting Antitumor Immunity after Allografting
增强同种异体移植后的抗肿瘤免疫力
- 批准号:
7575273 - 财政年份:2008
- 资助金额:
$ 51.46万 - 项目类别:
Augmenting Antitumor Immunity after Allografting
增强同种异体移植后的抗肿瘤免疫力
- 批准号:
7765518 - 财政年份:2008
- 资助金额:
$ 51.46万 - 项目类别:














{{item.name}}会员




