Investigating endothelial cell and glomerular anastomoses to advance kidney tissue engineering

研究内皮细胞和肾小球吻合以推进肾脏组织工程

• 批准号: 8967817
• 负责人: William Gee Chang
• 金额: $ 19.15万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8967817
• 关键词: Acid-Base Equilibrium; Address; Anastomosis - action; Apoptotic; Applications Grants; Award; BCL2 gene; Biological Assay; Biology; Blood; Blood Vessels; Cellular Spheroids; Clinical; Collagen; Collagen Type I; Communities; Development Plans; Device Designs; Devices; Dialysis procedure; Doctor of Philosophy; Drainage procedure; Electrolytes; Elements; End stage renal failure; Endothelial Cells; Engineering; Environment; Epithelial; Excretory function; Fellowship; Fibrin; Filtration; Funding; Future; Gel; Goals; Grant; Healthcare Systems; Human; Hydrogels; Immunodeficient Mouse; Implant; In Vitro; Instruction; Integrin Signaling Pathway; Integrins; Internal Medicine; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Knowledge; Laboratory Research; Liquid substance; Manuscripts; Mathematics; Mentors; Mentorship; Methodology; Microfluidic Microchips; Microfluidics; Morbidity - disease rate; Nephrology; Nephrons; Organ; Organ Donor; Pathway interactions; Patients; Pattern; Perfusion; Physicians; Process; Proteins; Rattus; Recruitment Activity; Renal Tissue; Research; Research Personnel; Research Project Grants; Residencies; Role; Scientist; Signal Transduction; Solutions; Structure; System; Techniques; Technology; Testing; Tissue Engineering; Tissues; Training; Transplantation; Tube; Tubular formation; United States; Universities; Vascular blood supply; Waiting Lists; Work; angiogenesis; arteriole; capillary bed; capsule; career; career development; design; implantation; improved; in vivo; insight; instructor; meetings; mortality; multidisciplinary; next generation sequencing; novel; novel strategies; programs; public health relevance; research study; responsible research conduct; skills; spatial relationship; symposium; transcriptome sequencing; urinary

 DESCRIPTION (provided by applicant): This K08 mentored career development application describes my four-year plan to complete my training as a physician scientist, combining practice in academic nephrology with an extramurally funded research program relevant to renal disease. More specifically, I propose to develop a research project and the skills necessary to become an independent investigator working in the field of kidney tissue engineering. Having completed an MD-PhD degree from NYU and internal medicine residency and nephrology fellowship at Yale, I maintain a strong desire to do research that impacts clinical problems. I am currently an Instructor in the Department of Internal Medicine at Yale. This K08 award would support the following goals: 1) to conduct renal tissue engineering research; 2) to develop expertise in tissue engineering and microfluidics; and 3) to develop an independent research career. End stage renal disease is a significant and costly problem best treated by kidney transplantation. However, there is a severe shortage of donor organs that could potentially be alleviated by tissue engineered kidney tissue. The functional unit of the kidney is called the nephron which has three primary components: 1) a blood supply 2) a filtration unit called a glomerulus and 3) a tubule to process the filtrate prior to excretion. Preliminary results demonstrated that implantation of endothelial cells with isolated renal glomeruli in vivo led to anastomoses and perfusion of microvessels and glomeruli. [The research proposed here seeks to further understand these anastomoses to significantly advance this renal tissue engineering strategy. Aim 1 is to investigate how glomeruli promote endothelial cell-glomerular anastomoses in vitro and in vivo. Knowledge derived from these studies may significantly improve the efficiency of anastomoses and ultimately glomerular survival and function. Aim 2 is to design a perfusable microfluidics device that supports the anastomoses and re-perfusion of glomeruli through microvascular networks in vitro. Microfluidics technology is featured prominently because I believe the ability to define the spatial relationships of the nephron structures will be necessary to incorporate tubular drainage of the perfused glomeruli in the future.] Key components of the career development plan include: 1) laboratory research driven by the research strategy described; 2) mentorship from a multidisciplinary group with expertise in vascular biology, tissue engineering, nephrology, and microfluidics; 3) participation in scientific conferences; 4) formal didactics in mathematics, microfluidics, and tissue engineering topics; and 5) supervised manuscript and grant submissions and instruction in responsible conduct of research. This career development plan will be carried out at Yale University, an outstanding environment that maintains an open, supportive community with state of the art facilities and a confluence of world-class researchers critical to the successful completion of this application.

 描述（由申请人提供）：这K 08辅导的职业发展应用程序描述了我的四年计划，以完成我作为一名医生科学家的培训，结合学术肾脏病学的实践与有关肾脏疾病的研究计划。更具体地说，我建议开发一个研究项目并获得成为肾脏组织工程领域独立研究者所需的技能。在完成了纽约大学的医学博士学位和耶鲁大学的内科住院医师和肾脏病学奖学金后，我保持着强烈的愿望，希望能做一些影响临床问题的研究。我目前是耶鲁大学内科系的讲师。该K 08奖项将支持以下目标：1）进行肾脏组织工程研究; 2）发展组织工程和微流体技术的专业知识; 3）发展独立的研究生涯。终末期肾病是一个重要的和昂贵的问题，最好的治疗方法是肾移植。然而，供体器官严重短缺，组织工程肾组织可能会缓解这一问题。肾脏的功能单位称为肾单位，其具有三个主要组成部分：1）血液供应，2）称为肾小球的过滤单元和3）在排泄之前处理滤液的小管。初步结果表明，内皮细胞与离体肾小球植入体内导致微血管和肾小球的闭塞和灌注。[The这里提出的研究寻求进一步理解这些疾病以显著地推进这种肾组织工程策略。目的1研究肾小球在体内外对内皮细胞-肾小球间质纤维化的促进作用。从这些研究中获得的知识可能会显着提高肾小球疾病的效率，并最终提高肾小球的存活率和功能。目的二是设计一种可灌注的微流体装置，通过体外微血管网络支持肾小球的栓塞和再灌注。微流体技术的特点突出，因为我相信，确定肾单位结构的空间关系的能力将是 在将来，需要将灌注肾小球的管状引流并入。职业发展计划的关键组成部分包括：1）由所述研究战略驱动的实验室研究; 2）来自血管生物学，组织工程，肾脏学和微流体学专业知识的多学科小组的指导; 3）参与科学研究。 会议; 4）数学，微流体和组织工程主题的正式教学法;和5）监督手稿和赠款提交和指导负责任的研究行为。这个职业发展计划将在耶鲁大学进行，这是一个优秀的环境，保持了一个开放的，支持性的社区，拥有最先进的设施和世界一流的研究人员的汇合，这对成功完成这项申请至关重要。