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

体外生产具有关节特征的组织工程化功能软骨仍然是一个挑战，体内软骨和骨软骨缺损的再生仍然是一个愿景。为了有效地解决这些问题，更好地了解微环境线索以及邻近细胞和组织界面对软骨前体细胞向软骨分化的调节影响是至关重要的。我们打算比较软骨/软骨下骨表面对间充质干细胞(MSCs)向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装置中，分化的软骨细胞和未分化的MSCs之间的直接细胞对细胞接触是否会促进分化，并改善再生组织的透明软骨样质量和生物力学性能。本研究旨在确定促进、阻止或干扰MSCs向软骨细胞分化的微环境条件，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，除了稳定再生组织的透明软骨表型外，抑制肥大和软骨内成骨途径是成功再生关节软骨组织的先决条件。

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.