Synthetic vascularization and regeneration in engineered tissues

工程组织中的合成血管化和再生

基本信息

批准号：
10566387
负责人：
SANGEETA N. BHATIA
金额：
$ 56.52万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
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：
2023-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10566387
关键词：
3-Dimensional Address Automobile Driving Biological Models Biology Blood Vessels Blood capillaries Buffers Cell Communication Cell Signaling Process Cells Clinical Communities Complex Disease Endothelial Cells Endothelium Endowment Engineering Engraftment Environment Experimental Models Fiber Fibroblasts Gene Expression Generations Goals Growth Hepatic Hepatic Tissue Hepatocyte Human Human Engineering Implant In Vitro Injury Life Liver Liver parenchyma Mediating Microfluidics Modeling Mus Natural regeneration Organ Organ Size Organ Transplantation Oxygen Paracrine Communication Pattern Perfusion Physiological Play Process Regenerative Medicine Regenerative capacity Regenerative engineering Research Personnel Role Signal Transduction Solid Stromal Cells System Systems Integration Technology Therapeutic Tissue Engineering Tissue Grafts Tissues Transplantation Variant Vascular blood supply Vascularization cell type density dosage efficacy testing fitness implantation improved in vitro Model in vivo in vivo Model innovative technologies insight intercellular communication liver injury liver transplantation novel strategies paracrine regenerative release factor response synthetic biology tool transcription factor vascular tissue engineering

项目摘要

Project Description The goal of this NEW PROJECT is to engineer liver tissue grafts in which the timing and extent of graft vascularization and expansion in a living host is directly manipulable. In vivo, cell-to-cell communication mediated through paracrine signals is a hallmark of multicellular life, and in the liver is thought to play a critical role in driving tissue vascularization and growth. In collaborative studies, the investigators have recently established experimental models of liver tissue that incorporate hepatocytes, endothelial cells, and stromal cells spatially patterned to bolster these cell-cell interactions. These interactions enable vascularization regenerative expansion of engineered human liver tissue both in vitro, in a microfluidic human liver model, and in vivo, in an ectopically implanted human liver graft. In this proposal, the investigators will build upon these model systems by leveraging synthetic transcription factors to take control over the dynamics of paracrine signaling within the engineered livers to enable controlled, on-demand tissue vascularization and expansion. The specific aims of this new proposal are: (1) To build functional vasculature in engineered tissue through synthetic vascularization, (2) To establish on-demand expansion of engineered functional liver tissue through synthetic regeneration, and (3) To develop approaches for system integration and robustness in suboptimal host environments. Together, leveraging both in vitro and in vivo models, these efforts will endow precise control of function, expansion, and engraftment of engineered vasculature and hepatic parenchyma and will more generally establish a new approach for synthetic control of engineered tissues that will advance engineered organ grafts closer towards clinical utility.

项目描述这个新项目的目的是设计时间和范围的肝组织移植活体宿主中的移植血管和扩张是直接操纵的。体内，细胞到细胞通过旁分泌信号介导的通信是多细胞生活的标志，在人们认为肝脏在驱动组织血管和生长中起着关键作用。合作研究，研究人员最近建立了肝组织的实验模型结合肝细胞，内皮细胞和基质细胞，以空间形式为增强这些细胞 - 细胞相互作用。这些相互作用使血管化的再生扩张在微流体的人肝模型和体内设计的人肝组织都在体外设计异位植入的人肝移植。在此提案中，调查人员将基于这些模型系统通过利用合成转录因子来控制工程肝内的旁分泌信号传导的动力学，以启用受控的按需组织血管形成和扩张。该新建议的具体目的是：（1）建造通过合成血管形成在工程组织中的功能性血管，（2）建立通过合成再生对工程功能性肝组织的按需扩展，（3）开发次优主机中系统集成和鲁棒性的方法环境。共同利用体外和体内模型，这些努力将赋予精确控制工程脉管系统和肝的功能，扩展和植入实质，通常会建立一种合成控制的新方法设计的组织将使工程的器官移植物更接近临床实用性。