Microengineered environments for epithelial-mesenchymal interactions (SysCODE 7

用于上皮间质相互作用的微工程环境（SysCODE 7

• 批准号: 8103047
• 负责人: Ali Khademhosseini
• 金额: $ 38.17万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8103047
• 关键词: 3-Dimensional; Abbreviations; Advanced Practice Nurse; American; Architecture; Basement membrane; Biochemical; Biological; Biological Process; Biology; Biomimetic Materials; Biomimetics; Bovine Serum Albumin; Cell Communication; Cells; Coculture Techniques; Collagen Type I; Complex; Cues; Development; Diabetes Mellitus; Dimensions; Discipline; Disease; EGF gene; Elements; Embryo; Engineering; Environment; Epidermal Growth Factor; Epithelial; Epithelial Cells; Ethylene Glycols; Extracellular Matrix; Fibroblast Growth Factor; Fibronectins; Fluorescein; Fluorescein-5-isothiocyanate; Generations; Genetic; Glycosaminoglycans; Goals; Green Fluorescent Proteins; Growth Factor; Heart Valves; Heart failure; High Pressure Liquid Chromatography; Histocompatibility Testing; Hyaluronic Acid; Hydrogels; Implant; In Vitro; Isothiocyanates; Lasers; Mesenchymal; Mesenchyme; Methods; Movement; Organ; Phosphate Buffer; Population; Population Study; Printing; Regenerative Medicine; Saline; Scanning Electron Microscopy; Science; Signal Transduction; Signaling Molecule; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; System; Techniques; Technology; Testing; Time; Tissue Engineering; Tissues; Tooth Diseases; Tooth Tissue; Transplantation; Tretinoin; Vascular Endothelial Growth Factors; Ventricular; Water; base; biological systems; bone morphogenetic protein 2; bone morphogenic protein; cell type; cellular engineering; combinatorial; design; ethylene glycol; in vivo; instrument; interest; novel; poly(dimethylsiloxane); semilunar valve; stem; tool; two-dimensional; ultraviolet

Diabetes and heart failure are diseases of enormous burden to Americans, and current therapies for these often-lethal diseases are clearly inadequate. The generation of organs suitable for transplantation offers tremendous potential to treat these types of diseases. The early development of over 20 mammalian organs involves the sequential, ordered exchange of signals between interacting epithelial and mesenchymal cell populations, resulting in their progressive differentiation. We hypothesize that this complex, dynamic regulatory network can be resolved by the integration of different scientific disciplines and used to design and build organ precursors or parts. As a part of the larger SysCODE consortium we will develop technologies that can be used to engineer the surrounding microenvironment. We propose to develop novel, three dimensional (3D) microscale constructs to be used as tools to study populations of interacting mesenchymal and epithelial cells . These microscale techniques will enable the biomimecry of the complex 3D structure of epithelial and mesenchymal cell interactions that occur in the embryonic in vivo environment. In vivo, the cellular environment is tightly regulated in 3D by interactions between cell-cell, cell-extracellular matrix (ECM) and cell-soluble factors. To effectively mimic mesenchymal and epithelial tissue we will engineer novel hydrogels embedded with cell types that resemble the cells native to these tissues. Addition features such as the basement membrane will also be engineered to fascilitate the movement of growth factors and environmental cues between the two types of tissue. This will all be accomplished through the successful completion of the following three Specific Aims: Aim 1: To develop biomimetic materials for engineering the cell-ECM interactions within 3D epithelial-mesenchymal constructs. Aim 2: To fabricate microscale constructs that can be used to study the interactions between epithelial and mesenchyme cell populations. Aim 3: To develop and validate a combinatorial approach to study microenvironmental factors in interacting epithelial and mesenchymal cell populations.

糖尿病和心力衰竭是对美国人的巨大负担的疾病，以及当前的疗法 通常，致命的疾病显然是不足的。适合移植的器官的产生 治疗这类疾病的巨大潜力。超过20多个哺乳动物器官的早期发展 涉及相互作用上皮和间质细胞之间信号的顺序交换 种群，导致他们的进行性分化。我们假设这个复杂的，动态的 可以通过整合不同的科学学科并用于设计监管网络 并建立器官前体或零件。 作为较大的Syscode联盟的一部分，我们将开发可用于设计的技术 周围的微环境。我们建议开发新颖的三维（3D）微观构建体 用作研究间质和上皮细胞的种群的工具。这些显微镜 技术将使上皮和间质细胞的复合物3D结构的仿生成分 在体内环境中发生的相互作用。在体内，细胞环境紧密 通过细胞 - 细胞，细胞 - 细胞基质（ECM）和细胞可溶性因子之间的相互作用在3D中调节。到 有效地模仿间质和上皮组织，我们将设计嵌入细胞的新型水凝胶 类型类似于这些组织的细胞。地下室膜等附加功能将 也可以设计为迷人的增长因素和环境线索的运动 组织类型。这一切都将通过成功完成以下三个完成 具体目的： 目的1：开发仿生材料，以设计3D中的细胞ECM相互作用 上皮间质构建体。 目标2：制造可用于研究之间相互作用的微观构造 上皮和间质细胞种群。 目标3：开发和验证一种研究微环境因素的组合方法 相互作用的上皮和间质细胞群体。

项目成果

Adult cardiac progenitor cell aggregates exhibit survival benefit both in vitro and in vivo.

• DOI: 10.1371/journal.pone.0050491
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Bauer M;Kang L;Qiu Y;Wu J;Peng M;Chen HH;Camci-Unal G;Bayomy AF;Sosnovik DE;Khademhosseini A;Liao R
• 通讯作者: Liao R