Autologous decellularized extracellular matrix promotes adipogenic differentiation of adipose derived stem cells in low serum culture system by regulating the ERK1/2-PPARγ pathway

Adipocyte. 2021 Dec;10(1):174-188. doi: 10.1080/21623945.2021.1906509.

Abstract

High viability and further adipogenic differentiation of adipose-derived stem cells (ADSCs) are fundamental for engraftment and growth of the transplanted adipose tissue. It has been demonstrated that extracellular matrix (ECM) regulates cell proliferation and differentiation by interacting with ERK1/2 signalling pathway. In this study, we prepared autologous decellularized extracellular matrix (d-ECM) and explored its effect on the proliferation and adipogenic ability of ADSCs in low serum culture. We found that 2% foetal bovine serum (FBS) in growth medium inhibited cell viability and DNA replication, and decreased mRNA and protein levels of PPARγ and C/EPBα compared with 10% FBS. Correspondingly, after 14-days adipogenic induction, cells cultured in 2% FBS possessed lower efficiency of adipogenesis and expressed less adipocyte differentiation markers ADIPOQ and aP2. On the contrary, the d-ECM-coated substrate continuously promoted the expression of PPARγ, and regulated the phosphorylation of ERK1/2 in different manners during differentiation. Pretreatment with ERK1/2 inhibitor PD98059 neutralized the effects of d-ECM, which suggested d-ECM might regulate the adipogenesis of ADSCs through ERK1/2-PPARγ pathway. In addition, d-ECM was revealed to regulate the transcription and expression of stemness-associated genes, such as OCT4, NANOG and SOX2, in the undifferentiated ADSCs, which might be related to the initiation of differentiation.

Keywords: Adipose-derived stem cells; ERK1/2-PPARγ pathway; adipogenic differentiation; cell proliferation; extracellular matrix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Adult
  • Cells, Cultured
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • PPAR gamma / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Young Adult

Substances

  • PPAR gamma
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Grants and funding

This research was funded by National Natural Science Foundation of China [81971850], Wenzhou Municipal Science and Technology Bureau [Y20190017], Wenzhou Municipal Science and Technology Bureau [Y20180148], and Wenzhou Municipal Science and Technology Bureau [Y2020085].