Low‐oxygen conditions promote synergistic increases in chondrogenesis during co‐culture of human osteoarthritic stem cells and chondrocytes

Abstract

There has been increased interest in co-cultures of stem cells and chondrocytes for cartilage tissue engineering as there are the limitations associated with using either cell type alone. Drawbacks associated with the use of chondrocytes include the limited numbers of cells available for isolation from damaged or diseased joints, their dedifferentiation during in vitro expansion, and a diminished capacity to synthesise cartilage-specific extracellular matrix components with age and disease. This has motivated the use of adult stem cells with either freshly isolated or culture-expanded chondrocytes for cartilage repair applications; however, the ideal combination of cells and environmental conditions for promoting robust chondrogenesis remains unclear. In this study, we compared the effect of combining a small number of freshly isolated or culture-expanded human chondrocytes with infrapatellar fat pad-derived stem cells (FPSCs) from osteoarthritic donors on chondrogenesis in altered oxygen (5% or 20%) and growth factor supplementation (TGF-β3 only or TGF-β3 and BMP-7) conditions. Both co-cultures, but particularly those including freshly isolated chondrocytes, were found to promote cell proliferation and enhanced matrix accumulation compared to the use of FPSCs alone, resulting in the development of a tissue that was compositionally more similar to that of the native articular cartilage. Local oxygen levels were found to impact chondrogenesis in co-cultures, with more robust increases in proteoglycan and collagen deposition observed at 5% O . Additionally, collagen type I synthesis was suppressed in co-cultures maintained at low-oxygen conditions. This study demonstrates that a co-culture of freshly isolated human chondrocytes and FPSCs promotes robust chondrogenesis and thus is a promising cell combination for cartilage tissue engineering.

Implantation of mesenchymal stem cells in combination with allogenic cartilage improves cartilage regeneration and clinical outcomes in patients with concomitant high tibial osteotomy

“…Sufficient cartilage regeneration is essential for avoiding continuous degradation of the articular surface, which can lead to degenerative arthritis of the knee joint despite the correction of varus knee malalignment during HTO. Although MSCs can differentiate into different specialized cell types, they tend to form a phenotypically unstable cartilaginous tissue with inferior biochemical and biomechanical properties compared to the native tissue [11]. Thus, it should be considered that the development of an advanced cell‐based tissue engineering approach using MSCs for cartilaginous lesions should address: (1) ability to repair with a mechanically stable hyaline cartilage‐like substance, (2) capacity to not deteriorate over time, and (3) sufficient integration with the surrounding tissue.…”

DMOG Negatively Impacts Tissue Engineered Cartilage Development

“…These results were not consistent with previous studies where low oxygen settings, such as chambers, were used, to enhance chondrogenesis. 15,20,21 The extracellular matrix attenuation in the DMOG treated tissue engineered cartilage were subsequently reflected in the mechanical properties of the tissue, which is the ultimate determination of tissue function.…”

Source and hub of inflammation: The infrapatellar fat pad and its interactions with articular tissues during knee osteoarthritis

“…Local hypoxic conditions are able to increase the expression and synthesis of proteoglycan and type II collagen when OA chondrocytes and OA-derived IFP-MSCs are cocultured, 44 indicating that cartilage regeneration may be facilitated by IFP-MSCs in response to stress triggers like hypoxic inflammatory microenvironments. 45 In addition to their chondroprotective effects, IFP-MSCs derived from OA patients may also contribute to degenerative cartilage alterations.…”