A 3D culture system for osteoarthritis chondrocytes

Abstract

Chondrocytes from cartilage tissues of osteoarthritis (OA) are abnormal cells that lost their function in maintaining the cartilage matrix. These cells are described as ‘‘dedifferentiated’’. Similarly, dedifferentiation is also observed in functioning mature chondrocytes upon monolayer culture, and it greatly affects the outcome of engineered tissues. In order to engineer functional cartilage tissues, a 3D culture platform with the ability to resume the phenotype of dedifferentiated cells and support redifferentiation is of great importance. We have developed in our lab a collagen microencapsulation technique that entraps cells in a condensed nanofibrous collagen meshwork, forming solid cell-collagen microspheres, which are a robust template for both mature cells and differentiating cells. Specifically, this system has been shown to support chondrogenic differentiation of stem cells and preserve the phenotypic characteristics of the subsequent chondrogenic lineages. These results prompted us to hypothesize that the system could also be appropriate for OA chondrocytes. In this study we aim to investigate the maintenance of chondrocytic phenotypes of chondrocytes isolated from OA patients in the 3D collagen microsphere system by taking reference to pellet and monolayer cultures. Results has been shown to be beneficial for OA chondrocytes phenotype maintenance and redifferentiation. OA Chondrocytes cultured in such way have a better expression of chondrogenic markers, especially in expressing SOX9, which is the master regulator in chondrogenesis.- With such benefits of collagen microencapsulation, chondrocytes isolated from OA patients could possibly be turned back to functional cells and serve various purposes such as drug screening models, pathology models and even implantable constructs.