Matrix stiffness regulates myocardial differentiation of human umbilical cord mesenchymal stem cells

Aging (Albany NY). 2020 Dec 9;13(2):2231-2250. doi: 10.18632/aging.202244. Epub 2020 Dec 9.

Abstract

Myocardial infarction is a cardiovascular disease with high mortality. Human umbilical cord mesenchymal stem cells (hUC-MSCs) with strong self-renewal capacity and multipotency, provide the possibility of replacing injured cardiomyocytes. hUC-MSCs were cultured on polyacrylamide hydrogels with stiffnesses corresponding to Young's modulus of 13-16kPa and 62-68kPa which mimic the stiffnesses of healthy heart tissue and fibrotic myocardium. The expression of early myocardial markers Nkx2.5, GATA4, Mesp1 and the mature myocardial markers cTnT, cTnI, α-actin were detected by RT-PCR and Western Blot, which showed that soft matrix (13-16 kPa) tended to induce the differentiation of hUC-MSCs into myocardium, compared with stiff matrix (62-68 kPa). Piezos are mechanically sensitive non-selective cation channels. The expression of Piezo1 increased with the stiffness gradient of 1-10kPa, 13-16kPa, 35-38kPa and 62-68kPa on the 1st day, but Piezo2 expression was irregular. The expression of integrin β1 and calcium ions were also higher on stiff substrate than on soft substrate. hUC-MSCs tend to differentiate into myocardium on the matrix stiffness of 13-16 kPa. The relationship among matrix stiffness, Piezo1 and myocardial differentiation needs further validation.

Keywords: Piezo1; human umbilical cord mesenchymal stem cells; integrin β1; matrix stiffness; myocardial differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Elastic Modulus
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • Hydrogels
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Myocardial Infarction / metabolism
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism*
  • Umbilical Cord / cytology*
  • Umbilical Cord / metabolism

Substances

  • Hydrogels