Microenviromental influence of cartilage and bone explants on chrondrogenic differentation of multipotent mesenchymal stem cells

软骨和骨外植体微环境对多能间充质干细胞慢性分化的影响

• 批准号: 71698147
• 负责人: Professorin Dr. Susanne Grässel
• 金额: --
• 依托单位: Abteilung Experimentelle Orthopädie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/71698147?language=en
• 关键词: Microenviromental; influence; cartilage; bone; explants

Ex vivo production of tissue-engineered functional cartilage with articular characteristics remains a challenge, in vivo regeneration of chondral and osteochondral defects remains still a vision. To effectively address the problems a better understanding of microenvironmental cues and the modulating influence of neighbouring cells and tissue interfaces on chondrogenic differentiation of chondroprogenitor cells are essential. We intend to compare impact of cartilage / subchondral bone surfaces on chondrogenic differentiation of mesenchymal stem cells (MSCs) and properties of regenerated tissue. Furthermore, we will test whether direct cell-to-cell contact between differentiated chondrocytes and undifferentiated MSCs in these experimental set ups will enhance differentiation and improve hyaline cartilage like quality and biomechanical properties of regenerated tissue. This study is designed to identify microenvironmental conditions which promote, prevent or interfere with chondrogenic differentiation of MSCs and to analyse their impact on molecular properties and quality of regenerated tissue. For MSC based cartilage repair, inhibition of hypertrophy and the endochondral ossification pathway in addition to stabilization of the hyaline cartilaginous phenotype of the regenerated tissue is a prerequisite for successful articular cartilage tissue regeneration.

体外制备具有关节特性的组织工程化功能软骨仍是一个挑战，体内再生软骨和骨软骨缺损仍是一个愿景。为了有效地解决这些问题，更好地了解微环境的线索和邻近细胞和组织界面对软骨祖细胞的软骨分化的调节影响是必不可少的。我们打算比较软骨/软骨下骨表面对间充质干细胞（MSCs）成软骨分化和再生组织特性的影响。此外，我们将测试在这些实验设置中分化的软骨细胞和未分化的MSC之间的直接细胞与细胞接触是否会增强分化并改善再生组织的透明软骨样质量和生物力学性质。本研究旨在确定促进，防止或干扰骨髓间充质干细胞软骨分化的微环境条件，并分析其对再生组织的分子特性和质量的影响。对于基于MSC的软骨修复，除了再生组织的透明软骨表型的稳定之外，抑制肥大和软骨内骨化途径是成功的关节软骨组织再生的先决条件。