Modifying consumptive coagulopathy following discordant porcine xenotransplantation - In vitro and in vivo analysis of enhanced HO-I expression on native and modified porcine cells and kidneys

改变不一致的猪异种移植后的消耗性凝血病 - 天然和修饰猪细胞和肾脏上增强的 HO-I 表达的体外和体内分析

基本信息

项目摘要

The aim of project IV is to analyse the aberrant activation of the human coagulation system following contact with porcine endothelium. For this purpose ex vivo porcine kidney and lung perfusion systems were modified to allow for analysis of coagulation activation parameters. The project will focus on the identification of potential targets for pharmacological abrogation of aberrant coagulation. Pharmacological intervention will be performed using different drugs acting at various levels of the coagulation process like Hirulog, activated protein C (APC), prostacyclin and nitroprusside. The administration of exogenous recombinant APC shall serve as a substitute for the non-functional porcine thrombomodulin to human thrombin interaction, which physiologically generates APC. Prostacyclin as well as Nitroprusside are aimed to cause inhibition of human platelet aggregation. Following identification of major incompatibilities susceptible to exogenous pharmacological intervention, alteration of these defects should be possible by introduction of appropriate human regulators of the coagulation cascade by rAAV mediated gene transfer or by genetic engineering. Finally, multi-transgenic porcine organs that had been engineered in a way to express human regulators of the coagulation system such as e.g. human thrombomodulin or HO-I will be tested in the perfusion circuits as to their ability to interfere with the aberrant coagulation activation in these systems.
项目IV的目的是分析与猪内皮细胞接触后人体凝血系统的异常激活。为此,对离体猪肾和肺灌注系统进行了修改,以允许分析凝血激活参数。该项目将侧重于确定异常凝血的药理学消除的潜在目标。将使用作用于凝血过程不同水平的不同药物进行药理学干预,如水蛭素、活化蛋白C(APC)、前列环素和硝普钠。外源性重组APC的施用应作为非功能性猪血栓调节蛋白与人凝血酶相互作用的替代物,其在生理上产生APC。前列环素和硝普钠旨在抑制人血小板聚集。在鉴定了对外源性药物干预敏感的主要不相容性后,通过rAAV介导的基因转移或基因工程引入适当的凝血级联调节剂,应该可以改变这些缺陷。最后,将在灌注回路中测试已经以表达凝血系统的人调节剂(例如人血栓调节蛋白或HO-1)的方式工程化的多转基因猪器官干扰这些系统中异常凝血激活的能力。

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 }}

Professor Dr. Michael Winkler其他文献

Professor Dr. Michael Winkler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('Professor Dr. Michael Winkler', 18)}}的其他基金

Emergence of structures and advantages in cross-diffusion systems
交叉扩散系统的结构和优点的出现
  • 批准号:
    411007140
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Analysis of chemotactic cross-diffusion in complex frameworks
复杂框架中趋化交叉扩散的分析
  • 批准号:
    288366228
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Editing Schleiermachers Lectures on Pedagogy and Psychology in the Critical Complete Edition
编辑施莱尔马赫的教育学和心理学讲座批判完整版
  • 批准号:
    207123114
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
    Research Grants
"Ausbildungsfähigkeit" - eine Diskursanalyse im erziehungswissenschaftlichen Publikationsraum
“培养能力”——教育科学出版空间的话语分析
  • 批准号:
    100104097
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Vorbereitung einer Edition von bisher unveröffentlichten Vorlesungsmitschriften der Pädagogik und Psychologie Friedrich Schleiermachers für die Kritische Gesamtausgabe (KGA) der Werke Schleiermachers; Transkription, EDV-Erfassung der Texte, textkritische
为弗里德里希·施莱尔马赫 (Friedrich Schleiermacher) 的著作批判完整版 (KGA) 准备先前未出版的教育学和心理学讲义版本;
  • 批准号:
    5147940
  • 财政年份:
    1999
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Fine structures in interpolation inequalities and application to parabolic problems
插值不等式的精细结构及其在抛物线问题中的应用
  • 批准号:
    462888149
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Existence and regularity theory and qualitative analysis
存在性规律理论与定性分析
  • 批准号:
    470900796
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Units

相似海外基金

Consumptive and non-consumptive effects of predators on prey in the northern boreal forest
北部北方森林捕食者对猎物的消耗性和非消耗性影响
  • 批准号:
    517984-2018
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Northern Research Supplement
Applying predation-risk theory to wildlife behaviour during non-consumptive ecotourism: grizzly bear viewing in Tweedsmuir Provincial Park, British Columbia
将捕食风险理论应用于非消耗性生态旅游期间的野生动物行为:在不列颠哥伦比亚省特威兹缪尔省立公园观赏灰熊
  • 批准号:
    546859-2020
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Ecology of fear: ecological and evolutionary consequences of non-consumptive effects of parasites
恐惧生态学:寄生虫非消耗性影响的生态和进化后果
  • 批准号:
    RGPAS-2020-00041
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Accelerator Supplements
Ecology of fear: ecological and evolutionary consequences of non-consumptive effects of parasites
恐惧生态学:寄生虫非消耗性影响的生态和进化后果
  • 批准号:
    RGPIN-2020-03910
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
The influence of food quality and quantity on non-consumptive predator effects
食物质量和数量对非消耗性捕食者效应的影响
  • 批准号:
    578378-2023
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Postdoctoral Fellowships
NETs targeting treatment for consumptive coagulopathy using H12-ADP-liposome
使用 H12-ADP-脂质体靶向治疗消耗性凝血病的 NET
  • 批准号:
    22H03179
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
New perspectives on the consumptive and non-consumptive effects of predators
关于掠食者的消耗性和非消耗性影响的新视角
  • 批准号:
    RGPIN-2018-06757
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
Japanese low-consumptive wildlife tourism: meaning and morality in hybrid online-offline spaces
日本低消费野生动物旅游:线上线下混合空间的意义和道德
  • 批准号:
    22F20797
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Japanese low-consumptive wildlife tourism: meaning and morality in hybrid online-offline spaces
日本低消费野生动物旅游:线上线下混合空间的意义和道德
  • 批准号:
    21F20797
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Ecology of fear: ecological and evolutionary consequences of non-consumptive effects of parasites
恐惧生态学:寄生虫非消耗性影响的生态和进化后果
  • 批准号:
    RGPIN-2020-03910
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了