Chondrocytes differentiated from human induced pluripotent stem cells: Response to ionizing radiation

PLoS One. 2018 Oct 23;13(10):e0205691. doi: 10.1371/journal.pone.0205691. eCollection 2018.

Abstract

Purpose: Data on the response of chondrocytes differentiated from hiPSCs (hiPSC-DCHs) to ionizing radiation (IR) are lacking. The aim of present study was to assess DNA damage response (DDR) mechanisms of IR-treated hiPSC-DCHs.

Methods and materials: The following IR-response characteristics in irradiated hiPSC-DCHs were assessed: 1) the kinetics of DNA DSB formation; 2) activation of major DNA repair mechanisms; 3) cell cycle changes and 4) reactive oxygen species (ROS), level of key markers of apoptosis and senescence.

Results: DNA DSBs were observed in 30% of the hiPSC-DCHs overall, and in 60% after high-dose (> 2 Gy) IR. Nevertheless, these cells displayed efficient DNA repair mechanisms, which reduced the DSBs over time until it reached 30% by activating key genes involved in homologous recombination and non-homologous end joining mechanisms. As similar to mature chondrocytes, irradiated hiPSC-DCH cells revealed accumulation of cells in G2 phase. Overall, the hiPSC-DCH cells were characterized by low levels of ROS, cPARP and high levels of senescence.

Conclusions: The chondrocyte-like cells derived from hiPSC demonstrated features characteristic of both mature chondrocytes and "parental" hiPSCs. The main difference between hiPSC-derived chondrocytes and hiPSCs and mature chondrocytes appears to be the more efficient DDR mechanism of hiPSC-DCHs. The unique properties of these cells suggest that they could potentially be used safely in regenerative medicine if these preliminary findings are confirmed in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / radiation effects*
  • Cell Line
  • Chondrocytes / physiology*
  • Chondrocytes / radiation effects
  • Chondrogenesis / radiation effects*
  • DNA Breaks, Double-Stranded / radiation effects
  • DNA End-Joining Repair / radiation effects
  • G2 Phase / radiation effects
  • Gamma Rays*
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Induced Pluripotent Stem Cells / radiation effects
  • Reactive Oxygen Species / metabolism
  • Regenerative Medicine / methods

Substances

  • Reactive Oxygen Species

Grant support

The present study was supported by the National Science Centre (grant no. 2012/07/E/NZ3/01819 (WMS) and UMO-2016/23/N/NZ7/01892 (ES)) and by the Greater Poland Cancer Centre (grant no. 13/2017(156) (EW)).