Chondrocyte De-Differentiation: Biophysical Cues to Nuclear Alterations.
Noor A Al-MaslamaniRachel A OldershawSimon TewJude CurranPieter D'HoogheKazuhiro YamamotoHenning F HornPublished in: Cells (2022)
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.
Keyphrases
- cell therapy
- induced apoptosis
- cell cycle arrest
- genome wide
- gene expression
- dna damage
- transcription factor
- stem cells
- mesenchymal stem cells
- total knee arthroplasty
- signaling pathway
- endoplasmic reticulum stress
- cell death
- extracellular matrix
- copy number
- cell proliferation
- platelet rich plasma
- fine needle aspiration