Human Chondrocytes

Chondrocytes are the only specialized cells that produce and maintain the extracellular matrix (ECM) in healthy cartilages. They only counts for 1-5% of a total cartilage tissue. Since cartilage is an avascular tissue, chondrocytes can only rely on diffusion of nutrients and metabolites from the articular surface. In order to accumulate with this low nutrient supply and hypoxia environment, chondrocytes inherently contains low mitochondrial numbers and low metabolic turnovers. Chondrocytes are derived from Mesenchymal Stem Cells (MSCs) through a process called chondrogenesis. Once chondrogenesis proceeds, chondroprogenitor cells, condensed from MSCs, express cartilage-specific collagens II, IX, and XI.

Morphologies of chondrocyte is controlled by its residence in cartilage. Chondrocytes in the superficial zone appears to have similar properties of mesenchymal stem cells. They have distinct spatial patterns in single cells, pairs, clusters or strings depending upon the joint type. Secretion of lubricin and hyaluronic acid at this area permits efficient gliding motion during joint movement. Moving deeper to the middle zone of cartilage, where chondrocytes are normally resting in a nonstressed steady state, type II collagen secreted by chondrocytes support the infrastructure of cartilage. The turnover of this type II collagen network is very slow, which has a half-life of 117 years. Deeper into the bone-adjacent area, cartilage here are calcified and has higher collagen X expression. The morphology of chondrocytes here turns rounder and large, expressing the hypertrophic characteristics, the terminal differentiation of chondrocytes.

Osteoarthrosis (OA) is an age-related chronic cartiage damage. Some studies show that chondrocyte senescence(aging and death) plays the most important role in OA development. Replacing cartilage with fresh chondrocytes seeded-scaffold or inject fresh chondrocytes may be a cure to OA, which has an estimated market value of $USD 25 billion worldwide. However, the major obstacle of chondrocyte therapy is the dedifferentiation phenomenon during lab expansion of cells. When primary chondrocytes are cultured in monolayer, they often undergo this process and lose their phenotype and their capacity to form cartilage. Constructing an efficient and safe chondrocyte cell bank is essential for chondrocyte therapy development and also a long-term plan of CBI for carrying out our ultimate goal-“Better care, better life.”

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