Tissue Engineering in Congenital Craniofacial Defects

先天性颅面缺陷的组织工程

基本信息

批准号：
7652360
负责人：
JENNIFER H ELISSEEFF
金额：
$ 38.13万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7652360
关键词：
Address Apert syndrome Area Biocompatible Materials Cell Line Cells Cephalic Chondrogenesis Coculture Techniques Congenital Abnormality Craniofacial Abnormalities Defect Development Diagnostic radiologic examination Disease Event FGFR2 gene Gene Expression Growth Growth Factor Histology Hydrogels In Vitro Investigation Kinetics Knock-in Mouse Knowledge Light Medicine Mesenchymal Stem Cells Modeling Morphology Mouse Cell Line Mus Musculoskeletal Mutant Strains Mice Mutation Natural regeneration Normal Cell Operative Surgical Procedures Osteogenesis Outcome Process Protein Secretion Proteomics Research Research Personnel Siblings Source System Technology Testing Tissue Engineering Tissues base cell behavior craniofacial craniofacial repair cranium design improved in vivo long bone minimally invasive monolayer mouse model multidisciplinary mutant novel novel strategies programs reconstruction repaired response scaffold

项目摘要

DESCRIPTION (provided by applicant): The long term objective of this research is to develop tissue engineering strategies for the understanding and treatment of craniofacial abnormalities. This proposal is both hypothesis and design driven. We will investigate tissue development of cells from mouse models of the craniofacial abnormality Apert syndrome. We hypothesize that mutant cells from the FGFR2 knock-in Apert mouse model developed by the co-Pi will develop tissue and respond to growth factors in a significantly different manner compared to normal cells when grown in monolayer or in three dimensional (3D) hydrogel scaffolds. Furthermore, we hypothesize that when the normal and mutant cells are cocultured in multilayered hydrogel scaffolds, proliferation, tissue development, and growth factor response will change. The design driven portion of the proposal will develop a clinically practical strategy for repair of craniofacial defects, in iatrogenic defects and in the disease mouse model, using cell encapsulation technologies developed by the lab. To test these hypotheses and design the repair system the following specific aims will be investigated: Specific aim 1. Investigate cell behavior and tissue development of cells isolated from FGFR2 knock-in mouse model of Apert Syndrome. Specifically this aim will address 1.) chondrogenesis and osteogenesis of cells from a Fgfr2+/S252W mouse model of Apert Syndrome, compared to cells from normal siblings and an immortalized, clonal mouse mesenchymal stem cell line. Cells from a.) the long bone and b.) the cranium will be evaluated in 2D monolayer and 3D hydrogel scaffolds in vitro. Specific aim 2. Investigate cell behavior and tissue development of mutant and normal cells in response to growth factors and co-culture. Specifically this aim will address 1.) response of mutant and normal cells to musculoskeletal-related growth factors in 2D and 3D hydrogel culture, and 2.) apply a novel 3D bilayered hydrogel system to coculture normal and mutant cells to determine the effects of coculture on cell behavior and tissue development of normal and mutant cells. Specific aim 3. Determine in vivo function of mutant and normal cells in craniofacial models. Specifically, tissue development in 1.) iatrogenic mouse cranial defects and 2.) congenital defects in Apert Syndrome will be evaluated using cells embedded in hydrogels. Normal and mutant mouse cell lines will be used in addition to a clonally-derived mouse mesenchymal stem cell line. Tissue development will be assessed by radiographic and histological analyses.

描述（由申请人提供）：本研究的长期目标是开发组织工程策略来理解和治疗颅面异常。该提案是假设和设计驱动的。我们将研究颅面异常阿佩尔综合征小鼠模型细胞的组织发育。我们假设，当在单层或三维 (3D) 水凝胶支架中生长时，co-Pi 开发的 FGFR2 敲入 Apert 小鼠模型中的突变细胞将发育组织并以与正常细胞显着不同的方式对生长因子作出反应。。此外，我们假设当正常细胞和突变细胞在多层水凝胶支架中共培养时，增殖、组织发育和生长因子反应将会改变。该提案的设计驱动部分将利用实验室开发的细胞封装技术，开发一种临床实用策略，用于修复颅面缺陷、医源性缺陷和疾病小鼠模型。为了测试这些假设并设计修复系统，将研究以下具体目标：具体目标 1. 研究从阿珀特综合征 FGFR2 敲入小鼠模型中分离的细胞的细胞行为和组织发育。具体而言，该目标将解决 1.) 与来自正常兄弟姐妹和永生化克隆小鼠间充质干细胞系的细胞相比，来自阿珀特综合征 Fgfr2+/S252W 小鼠模型的细胞的软骨形成和成骨。来自 a.) 长骨和 b.) 颅骨的细胞将在体外 2D 单层和 3D 水凝胶支架中进行评估。具体目标 2. 研究突变细胞和正常细胞对生长因子和共培养的反应和组织发育。具体而言，该目标将解决 1.) 2D 和 3D 水凝胶培养中突变细胞和正常细胞对肌肉骨骼相关生长因子的反应，以及 2.) 应用新型 3D 双层水凝胶系统共培养正常细胞和突变细胞以确定共培养的效果正常细胞和突变细胞的细胞行为和组织发育。具体目标3.确定颅面模型中突变细胞和正常细胞的体内功能。具体来说，将使用嵌入水凝胶中的细胞来评估 1.) 医源性小鼠颅骨缺陷和 2.) 阿佩尔综合征先天性缺陷的组织发育。除了克隆衍生的小鼠间充质干细胞系之外，还将使用正常和突变的小鼠细胞系。将通过放射线照相和组织学分析评估组织发育。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

PEG hydrogel degradation and the role of the surrounding tissue environment.

DOI：
10.1002/term.1688
发表时间：
2015-03
期刊：
Journal of tissue engineering and regenerative medicine
影响因子：
3.3
作者：
Reid B;Gibson M;Singh A;Taube J;Furlong C;Murcia M;Elisseeff J
通讯作者：
Elisseeff J

The study of abnormal bone development in the Apert syndrome Fgfr2+/S252W mouse using a 3D hydrogel culture model.

使用 3D 水凝胶培养模型研究阿佩尔综合征 Fgfr2 /S252W 小鼠骨发育异常。

DOI：
10.1016/j.bone.2008.02.008
发表时间：
2008
期刊：
Bone
影响因子：
4.1
作者：
Yang,Fan;Wang,Yingli;Zhang,Zijun;Hsu,Bryan;Jabs,EthylinWang;Elisseeff,JenniferH
通讯作者：
Elisseeff,JenniferH

An injectable adipose matrix for soft-tissue reconstruction.