A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing

用于肾脏疾病建模和药效测试的微生理系统

基本信息

  • 批准号:
    9757837
  • 负责人:
  • 金额:
    $ 22.52万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-25 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Chronic kidney disease is a public health problem affecting more than 20 million people in the US adult population, and is the 9th leading cause of death. Few drugs other than renin-angiotensin system inhibitors slow the progression of kidney disease, lower mortality rates, or improve quality of life among people. New strategies targeting the early stages of these underlying diseases are fundamentally important to improve outcomes and patient care. To catalyze the development of drugs that are safe and effective for treating kidney diseases, there is a critical need to be able to model human kidney diseases and injury in vitro during preclinical drug development. The complex multicellular architecture and unusual triad of physiological processes characterized by glomerular filtration, tubular secretion and tubular reabsorption, have often limited the ability of whole organism models to fully recapitulate the diversity and manifestations of human disease. Conventional two-dimensional human epithelial cell models do not accurately recapitulate kidney physiology or disease, and microfluidic flow is essential to kidney nephron structure and function, and is an essential component in recapitulating in vivo physiology and pathophysiology. We have developed a three dimensional flow directed “kidney-on-a-chip” microphysiological system populated with human kidney cells, which has been extensively tested with functional characterization of key component structures of the proximal tubule and the peritubular microvascular network. We are also able to routinely obtain, isolate and characterize relatively pure primary cultures of multiple human kidney cell lineages. In addition, we have developed hydrogels consisting of decellularized human kidney cortical extracellular matrix, and demonstrated phenotypic differences when human kidney cells are grown in this matrix. In addition, we have recently incorporated the use of human pluripotent stem cells coupled with gene editing techniques into our MPS. Our platforms allow for precise control of cellular composition, extracellular matrix, and vascular and tubular geometry and flow. The goal of this application is to model important human kidney diseases and promote identification of safe and effective treatments. To achieve this goal, we have established a multidisciplinary investigative team with expertise in kidney physiology and pathology, cellular and molecular biology, systems pharmacology and toxicology, biomarker discovery and evaluation, biomedical engineering, microfluidics, matrix biology, genomics, computational biology, and biostatistics. If successful, ultimately in vitro models that recapitulate critical aspects of kidney physiological function, response to injury, and repair could contribute greatly to drug discovery and development, and could ultimately enable `virtual clinical trials' for candidate therapeutics.
项目总结

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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Jonathan Himmelfarb其他文献

Jonathan Himmelfarb的其他文献

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{{ truncateString('Jonathan Himmelfarb', 18)}}的其他基金

Central Hub for Kidney Precision Medicine
肾脏精准医学中心中心
  • 批准号:
    10706473
  • 财政年份:
    2022
  • 资助金额:
    $ 22.52万
  • 项目类别:
KPMP Kidney Mapping and Atlas Project (KMAP)
KPMP 肾脏绘图和图集项目 (KMAP)
  • 批准号:
    10492787
  • 财政年份:
    2022
  • 资助金额:
    $ 22.52万
  • 项目类别:
KPMP Kidney Mapping and Atlas Project (KMAP)
KPMP 肾脏绘图和图谱项目 (KMAP)
  • 批准号:
    10705740
  • 财政年份:
    2022
  • 资助金额:
    $ 22.52万
  • 项目类别:
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems
使用芯片肾微生理系统进行人体临床试验的安全性和有效性
  • 批准号:
    10037553
  • 财政年份:
    2020
  • 资助金额:
    $ 22.52万
  • 项目类别:
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems
使用芯片肾微生理系统进行人体临床试验的安全性和有效性
  • 批准号:
    10671573
  • 财政年份:
    2020
  • 资助金额:
    $ 22.52万
  • 项目类别:
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems
使用芯片肾微生理系统进行人体临床试验的安全性和有效性
  • 批准号:
    10216377
  • 财政年份:
    2020
  • 资助金额:
    $ 22.52万
  • 项目类别:
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems
使用芯片肾微生理系统进行人体临床试验的安全性和有效性
  • 批准号:
    10515788
  • 财政年份:
    2020
  • 资助金额:
    $ 22.52万
  • 项目类别:
Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems
使用芯片肾微生理系统进行人体临床试验的安全性和有效性
  • 批准号:
    10471014
  • 财政年份:
    2020
  • 资助金额:
    $ 22.52万
  • 项目类别:
Effects of microgravity on the structure and function of proximal and distal tubule MPS
微重力对近远曲小管MPS结构和功能的影响
  • 批准号:
    9890028
  • 财政年份:
    2017
  • 资助金额:
    $ 22.52万
  • 项目类别:
A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing
用于肾脏疾病建模和药效测试的微生理系统
  • 批准号:
    9975953
  • 财政年份:
    2017
  • 资助金额:
    $ 22.52万
  • 项目类别:

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