3D in vitro Model System with Perfused Human Capillaries for Tissue Engineering

用于组织工程的具有灌注人体毛细血管的 3D 体外模型系统

• 批准号: 8061395
• 负责人: Monica Lizet Moya
• 金额: $ 4.84万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-14 至 2014-02-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8061395
• 关键词: Address; Adipocytes; Adipose tissue; Angiogenic Factor; Animals; Anti-Obesity Agents; Area; Beds; Biological Models; Blood Circulation; Blood Vessels; Blood capillaries; Cardiovascular Diseases; Cell Culture Techniques; Cell Survival; Cells; Characteristics; Comorbidity; Complex; Congenital Abnormality; Controlled Environment; Coupled; Development; Devices; Diabetes Mellitus; Dimensions; Discipline; Elements; Endothelial Cells; Engineering; Environment; Excision; Fellowship; Figs - dietary; Goals; Growth; Health Expenditures; Human; Imaging technology; In Vitro; Knowledge; Length; Link; Lipoatrophy; Liquid substance; Malignant Neoplasms; Microfabrication; Microfluidic Microchips; Modeling; Molecular; Morphology; Neoplasm Metastasis; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pathologic Processes; Perfusion; Permeability; Process; Reproducibility; Research; Research Training; Risk Factors; Role; Screening procedure; Stromal Cells; Surface; System; Techniques; Technology; Therapeutic; Tissue Engineering; Tissues; Translating; Translations; Trauma; adipokines; angiogenesis; base; capillary; cell stroma; density; design; human disease; human tissue; in vitro Model; in vivo; insight; lipid biosynthesis; neovascularization; novel; optical imaging; pressure; response; success; tumor

DESCRIPTION (provided by applicant): The growth of adipose tissue is tightly coupled with neovascularization. Understanding of such relationship is key for the design of anti-obesity therapeutics or conversely for the engineering of vascularized adipose tissue which could eventually serve as a material for use in the replacement of lost or damaged tissue due to tumor removal, trauma, lipoatrophy, or congenital defects. Although in vitro studies have led to the identification of many angiogenic factors in adipose tissue, as well as adipokines, there is still a paucity of knowledge about the dynamic relationship between adipocytes, stromal cells, and endothelial cells. In vivo animal studies have provided some insight into the concomitant process of angiogenesis and adipogenesis, but many of these models require translation to humans. In this proposed research training fellowship, the design of a novel 3D in vitro system with perfused human capillaries that can be useful for enhancing the fundamental understanding of these two processes is presented. For this system the fusion of microfabrication techniques with 3D cell culture will be used to create a microfludic device consisting of two fluid-filled microfabricated microchannels separated by metabolically active tissue. Once the device has been constructed and characterized, preadipocytes will be introduced into the microtissue and the simultaneous formation of angiogenesis with adipogenesis will be investigated. It is hypothesized that adipocytes can regulate new vasculature and participate in new vessel formation structurally, impacting both permeability and vessel growth PUBLIC HEALTH RELEVANCE: This research training proposal is driven by the objective of creating a 3D in vitro system with perfused human capillaries that will enhance the fundamental understanding of angiogenesis and adipogenesis. Obesity is a major risk factor for the development of many several prevalent and costly human diseases such as Type 2 diabetes, cardiovascular disease and cancer, all of which are linked to angiogenesis. The results of this proposal could facilitate the design of better therapies to reduce or cure obesity and its associated co- morbidities, and thus significantly reduce health care expenditures. .

描述（由申请方提供）：脂肪组织的生长与新血管形成紧密相关。理解这种关系对于设计抗肥胖治疗剂或相反地对于血管化脂肪组织的工程化是关键的，所述血管化脂肪组织最终可以用作用于替换由于肿瘤去除、创伤、脂肪萎缩或先天性缺陷而损失或受损的组织的材料。虽然在体外研究已经导致了许多血管生成因子在脂肪组织中的识别，以及脂肪因子，仍然是一个缺乏知识的动态脂肪细胞，基质细胞和内皮细胞之间的关系。在体内动物研究提供了一些洞察血管生成和脂肪形成的伴随过程，但许多这些模型需要翻译到人类。在这项拟议的研究培训奖学金中，提出了一种新型的3D体外系统的设计，该系统具有灌注的人体毛细血管，可用于增强对这两个过程的基本理解。对于该系统，微制造技术与3D细胞培养的融合将用于创建由两个由代谢活性组织分离的流体填充的微制造微通道组成的微流体装置。一旦该装置已经构建和表征，前脂肪细胞将被引入到微组织中，并将研究血管生成与脂肪生成的同时形成。假设脂肪细胞可以调节新的血管系统，并在结构上参与新血管的形成，影响渗透性和血管生长 公共卫生相关性：这项研究培训计划的目标是创建一个具有灌注人体毛细血管的3D体外系统，这将增强对血管生成和脂肪生成的基本理解。肥胖是许多流行和昂贵的人类疾病如2型糖尿病、心血管疾病和癌症发展的主要风险因素，所有这些疾病都与血管生成有关。该提案的结果可以促进设计更好的疗法来减少或治愈肥胖及其相关的共病，从而显著降低医疗保健支出。 .