Biomimetic Scaffolds to Promote Stem Cell Differentiation for Cartilage Engineeri

仿生支架促进软骨工程干细胞分化

基本信息

批准号：
8837570
负责人：
Julie C. Liu
金额：
$ 19.78万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-11 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8837570
关键词：
Address Adult Affect American Arthritis Biomimetics Cartilage Cartilage Matrix Cattle Cells Chondrocytes Chondrogenesis Chondroitin Sulfates Clinical Collagen Collagen Type II Coupled Cues Data Defect Degenerative polyarthritis Development Disease Environment Enzymes Extracellular Matrix Foundations Future Gene Expression Glycosaminoglycans Goals Harvest Health Human Hyaluronic Acid Hyaluronidase Inflammation Injury Interleukin-1 Joints Lead Matrix Metalloproteinases Mechanics Mediating Mesenchymal Stem Cells Mind Modeling Morbidity - disease rate Oryctolagus cuniculus Pain Peptides Process Production Property Site Source Structure Symptoms Technology Testing Tissue Engineering United States National Institutes of Health adult stem cell aggrecan aggrecanase articular cartilage base bone morphogenetic protein 2 cartilage degradation cartilage regeneration cartilage repair cytokine design functional mimics improved in vivo joint function joint stiffness polysulfated glycosaminoglycan prevent research study scaffold stem cell differentiation tissue regeneration

项目摘要

DESCRIPTION: Osteoarthritis (OA) is a debilitating disease that, according to the Arthritis Foundation, affects over 27 million Americans. The disease is characterized by a breakdown of articular cartilage extracellular matrix (ECM) molecules, including collagen type II, aggrecan, and hyaluronic acid (HA). As the ECM degrades, symptoms appear including pain and increasing joint stiffness. Once loss of collagen occurs, it is believed that the opportunity for unaided cartilage regeneration is lost. With this in mind, we previously described synergistic effects of combining a functional mimic of aggrecan with aligned cartilage to prevent matrix degradation and promote cartilage ECM synthesis by primary bovine chondrocytes. However, in humans, we are limited in our supply of chondrocytes, and harvest of primary articular chondrocytes can lead to donor site morbidity. Adult mesenchymal stem cells (MSCs) are a promising cell source because they can be harvested without injury, have a high proliferation capacity, and can differentiate into chondrocytes under appropriate environmental conditions. One major challenge of utilizing MSCs, however, is that grafts seeded with MSCs do not produce as much matrix as grafts seeded with differentiated chondrocytes. Thus, it is vital to establish conditions for effective differentiation and subsequent matrix production. Our long-term goal is to use MSCs in tissue-engineered cartilage to replace cartilage damaged by osteoarthritis. To achieve this goal, our objective is to create an environment that resists the destructive cycle of cartilage degradation from OA, mimics the native cartilage structure, and promotes chondrogenic differentiation of MSCs. To address these issues, we have developed the following specific aims. Aim 1: Evaluate the effects of alignment, aggrecan mimic concentration, and BMP peptide concentration on stem cell differentiation. Aim 2: Investigate the effect of synergistic interactions on cartilage differentiation. The results from this applicaton will elucidate properties of the local microenvironment that affect stem cell differentiation, resulting in enhanced matrix production and mechanical properties. These studies will thus serve as preliminary data for a future NIH R01 application that will evaluate these constructs in an in vivo defect model. Identification of material-based cues that result in improved cartilage grafts is essential in the development of safe and effective clinical therapies involving adult ste cells.

描述：骨关节炎（OA）是一种使人衰弱的疾病，根据关节炎基金会的说法，它影响了超过2700万美国人。该疾病的特征是关节软骨细胞外基质（ECM）分子（包括II型胶原蛋白，脂肪蛋白酶）和透明质酸（HA）的分解。随着ECM的降解，症状似乎包括疼痛和关节刚度的增加。一旦失去胶原蛋白，人们相信失去了无助的软骨再生的机会。考虑到这一点，我们先前描述了将Aggrecan的功能模仿与对齐软骨相结合以防止基质降解并促进原代牛软骨细胞合成软骨ECM合成的协同作用。但是，在人类中，我们的软骨细胞供应受到限制，而原发关节软骨细胞的收获会导致供体部位的发病率。成年间充质干细胞（MSC）是一种有前途的细胞来源，因为它们可以在不损伤的情况下收获，具有很高的增殖能力，并且可以在适当的环境条件下区分为软骨细胞。但是，利用MSC的一个主要挑战是，用MSC播种的移植物不会产生与用分化软骨细胞接种的移植物一样多的基质。因此，建立有效分化和随后的基质产生的条件至关重要。我们的长期目标是在组织工程的软骨中使用MSCs来代替因骨关节炎而损害的软骨。为了实现这一目标，我们的目标是创建一个环境，以抵抗软骨降解的破坏性循环，从OA中，模仿天然软骨结构，并促进MSC的软骨分化。为了解决这些问题，我们已经开发了以下特定目标。 AIM 1：评估比对，AggreCan模拟浓度和BMP肽浓度对干细胞分化的影响。目标2：研究协同相互作用对软骨分化的影响。该应用的结果将阐明影响干细胞分化的局部微环境的性质，从而增强基质产生和机械性能。因此，这些研究将作为未来NIH R01应用程序的初步数据，该数据将在体内缺陷模型中评估这些构建体。鉴定基于材料的线索可改善软骨移植物，这对于开发涉及成年Ste细胞的安全有效临床疗法至关重要。