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A Modular Niche-Based Approach to Soft Tissue Regeneration

基于模块化生态位的软组织再生方法

基本信息

批准号：
7849715
负责人：
ADAM J. KATZ
金额：
$ 22.12万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7849715
关键词：
3-Dimensional Adherent Culture Adipose tissue Arts Autologous Biological Cell Survival Cells Cellular Structures Cellular biology Development Discipline Engraftment Extracellular Matrix Fatty acid glycerol esters Goals Human Implant In Vitro Injury Literature Maintenance Methods Molecular Morbidity - disease rate NOD/SCID mouse Natural regeneration Operative Surgical Procedures Organoids Outcome Pericytes Proteins Regenerative Medicine Reporting Risk Role Science Serum Site Stem cells Suspension Culture Suspension substance Suspensions System Techniques Time Tissue Engineering Trauma Treatment Efficacy Work Wound Healing base flexibility human disease in vivo in vivo Model insight lipid biosynthesis mouse model novel novel strategies obesity treatment public health relevance regenerative scaffold soft tissue stem cell differentiation tissue reconstruction tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of this work is to develop predictable and reproducible therapies for soft tissue regeneration using adipose stem cells (ASCs) formulated as 3-dimensional (3-D) multicellular aggregates. Currently available treatments are limited by risk, morbidities, and/or reliability. Cell based tissue engineering strategies are quickly emerging as a promising approach to adipose tissue replacement and regeneration, with a goal to provide platforms based on scientific principles. In addition to providing a novel approach to adipose tissue regeneration, this work will also generate in vitro and in vivo models that will be of use for understanding obesity and the treatment thereof, as well as the biology of cell niches and the role of the micro-milieu in controlling cell survival and fate. Aim 1 studies will characterize the effect of serum-free 3-D suspension culture on ASC differentiation in vitro, yielding a defined system that will enable further mechanistic studies. Aim 2 studies will characterize how 3-D suspension culture impacts ASC survival and adipogenic differentiation in vivo using a NOD SCID mouse model. Aim 3 studies will characterize the impact of recipient site (milieu) on the engraftment and differentiation of ASCs prepared and delivered as multicellular aggregates. Together, these studies will provide insights as to how culture method (i.e. 3-D suspension culture, serum-free medium) influences the biological activity and therapeutic efficacy of ASCs. PUBLIC HEALTH RELEVANCE Cell-based regenerative medicine strategies hold tremendous potential for the treatment of human disease and trauma. However, this emerging discipline is in need of techniques and methods that enable reproducible and predictable outcomes. This proposal will pursue a novel `modular' approach to soft tissue reconstruction/regeneration using prefabricated multicellular aggregates that approximate cell structures reported in the literature to be responsible for normal adipose tissue development.

描述（由申请人提供）：这项工作的长期目标是使用配制为三维（3-D）多细胞聚集体的脂肪干细胞（ASC）开发可预测和可重复的软组织再生疗法。目前可用的治疗受到风险、发病率和/或可靠性的限制。基于细胞的组织工程策略正在迅速成为脂肪组织替代和再生的有前途的方法，其目标是提供基于科学原理的平台。除了提供脂肪组织再生的新方法外，这项工作还将产生体外和体内模型，这些模型将用于理解肥胖及其治疗，以及细胞小生境的生物学和微环境在控制细胞存活和命运中的作用。目标1研究将表征无血清3D悬浮培养对体外ASC分化的影响，产生一个定义的系统，从而能够进行进一步的机制研究。目的2研究将使用NOD SCID小鼠模型来表征3-D悬浮培养如何影响ASC存活和体内脂肪形成分化。目的3研究将表征受体部位（环境）对作为多细胞聚集体制备和递送的ASC的植入和分化的影响。总之，这些研究将提供有关培养方法（即3-D悬浮培养，无血清培养基）如何影响ASC的生物活性和治疗功效的见解。基于细胞的再生医学策略在治疗人类疾病和创伤方面具有巨大的潜力。然而，这一新兴学科需要能够实现可重复和可预测结果的技术和方法。该提案将采用一种新的“模块化”方法，使用预制的多细胞聚集体进行软组织重建/再生，这些聚集体近似于文献中报道的负责正常脂肪组织发育的细胞结构。