Age related changes in cell stiffness of tendon stem/progenitor cells and a rejuvenating effect of ROCK-inhibition

Biochem Biophys Res Commun. 2019 Feb 12;509(3):839-844. doi: 10.1016/j.bbrc.2019.01.027. Epub 2019 Jan 11.

Abstract

Tendon stem/progenitor cells (TSPC) are potential targets for regenerative medicine and the treatment of tendon injuries. The frequency of such injuries increases in elderly patients while the proportion of functional TSPCs in tendon tissue decreases, protracting tendon repair. Using atomic force microscopy (AFM), we show that cell stiffness and size increase in TSPCs isolated from elderly patients (A-TSPC) compared to TSPCs from younger patients (Y-TSPC). Additionally, two-photon excited fluorescence (TPEF) microscopy revealed a denser, well-structured actin cytoskeleton in A-TSPC, which correlates with the augmented cell stiffness. Treating A-TSPC with ROCK-inhibitor, reverses these age-related changes, and has rejuvenating effect on cell morphology and stiffness. We assume that cellular stiffness is a suitable marker for cell aging and ROCK a potential target for therapeutic applications of cell rejuvenation.

Keywords: Cell aging; Elastic modulus; ROCK-inhibition; Rejuvenation; hTSPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides / pharmacology*
  • Biomechanical Phenomena / drug effects
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Size / drug effects
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Elastic Modulus / drug effects
  • Humans
  • Middle Aged
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / pharmacology*
  • Rejuvenation
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tendons / cytology*
  • Tendons / drug effects
  • Tendons / metabolism
  • Young Adult
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Amides
  • Protein Kinase Inhibitors
  • Pyridines
  • Y 27632
  • rho-Associated Kinases