Non-contact Coculture Reveals a Comprehensive Response of Chondrocytes Induced by Mesenchymal Stem Cells Through Trophic Secretion

Abstract

Coculture between mesenchymal stem cells (MSCs) and chondrocytes has significant implications in cartilage regeneration. However, a conclusive understanding remains elusive. Previously, we reported that rabbit bone marrowderived MSCs (rbBMSCs) could downregulate the differentiated phenotype of rabbit articular chondrocytes (rbACs) in a non-contact coculture system for the first time. In the present study, a systemic investigation was performed to understand the biological characteristics of chondrocytes in coculture with MSCs. Firstly, cells (MSCs and chondrocytes) from different origins were cocultured in transwell system. Different chondrocytes, when cocultured with different MSCs respectively, consistently demonstrated stimulated proliferation, transformed morphology and declined glycosaminoglycan secretion of chondrocytes. Next, cell surface molecules and the global gene expression of rbACs were characterized. It was found that cocultured rbACs showed a distinct surface molecule profile and global gene expression compared to both dedifferentiated rbACs and rbBMSCs. In the end, cocultured rbACs were passaged and induced to undergo the chondrogenic redifferentiation. Better growth and chondrogenesis ability were confirmed compared with control cells without coculture. Together, chondrocytes display comprehensive changes in coculture with MSCs and the cocultured rbACs are beneficial for cartilage repair.

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“…MSCs in 3D microniches co-cultured with chondrocytes showed GO terms relating to ribosome biogenesis, ECM organization, and positive regulation of cell migration and glycosaminoglycan binding, processes which were similar to those encountered in MSC chondrogenesis [ 70 ]. Chondrocytes in the 3D group showed significant variations in gene expression relating to cellular processes, ECM, and signal transduction, suggesting a comprehensive response that was also observed in other studies using rabbit chondrocytes [ 71 ]. A number of cartilage-related GO terms for both MSCs and chondrocytes in the 3D group suggested that MSCs cultured in microniches had greater potential to maintain in vitro chondrogenesis and maintenance of the original chondrocyte phenotype.…”