Chondrocyte De-Differentiation: Biophysical Cues to Nuclear Alterations

Abstract

Autologous chondrocyte implantation (ACI) is a cell therapy to repair cartilage defects. In ACI a biopsy is taken from a non-load bearing area of the knee and expanded in-vitro. The expansion process provides the benefit of generating a large number of cells required for implantation; however, during the expansion these cells de-differentiate and lose their chondrocyte phenotype. In this review we focus on examining the de-differentiation phenotype from a mechanobiology and biophysical perspective, highlighting some of the nuclear mechanics and chromatin changes in chondrocytes seen during the expansion process and how this relates to the gene expression profile. We propose that manipulating chondrocyte nuclear architecture and chromatin organization will highlight mechanisms that will help to preserve the chondrocyte phenotype.

Characterization of Composite Agarose-Collagen Hydrogels for Chondrocyte Culture

“…The average nuclei diameter observed resembles dimensions of chondrocyte nuclei reported at earlier time frames of culture 28,54,55 and aspect ratios remain circular-like in 2-dimensional images after 21 days in culture (Figure S2), indicating the hydrogel material is not significantly influencing the cells to dedifferentiate and may be suitable in preventing terminal differentiation 56 . While it is well established that cells are sensitive to substrate stiffnesses in 2-dimensional culture [57][58][59][60] , the influence of substrate stiffness is less understood in 3-dimensional culture 61 .…”

Articular cartilage repair biomaterials: strategies and applications

“…Cartilage is crucial in providing mechanical support, absorbing pressure and shock, dispersing pressure, buffering shock absorption, and reducing joint friction [ 57 ]. Due to its unique physical properties, cartilage can maintain structural integrity even under heavy loads [ 58 ]. However, cartilage damage resulting from trauma or osteoarthritis requires biomaterials with mechanical properties and excellent physical structure to provide force support [ 59 , 60 ].…”