Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix

Yun Sun, Weiping Li, Zhengding Lu, Richard Chen, Jian Ling, Qitao Ran, Robert L. Jilka, Xiao Dong Chen

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

This study aimed to determine whether aging negatively affects MSC replication and osteogenesis and whether these features could be altered by exposure to an extracellular matrix (ECM) generated by marrow cells from young or old mice. A cell-free ECM was prepared from cultured femoral marrow cells from either 3- or 18-mo-old C57BL/6 mice (young-ECM or old-ECM, respectively). The replication and osteogenesis of young or old MSCs maintained on young- ECM vs. old-ECM as well as plastic were examined in vitro and in vivo. We found that the frequency of MSCs in marrow from old mice, measured by colony-forming cells, was only marginally lower than that of young mice. In contrast, defects in the self-renewal and bone formation capacity of old MSCs were remarkable. These defects were corrected by provision of a young- ECM but not old-ECM. In parallel cultures maintained on a young-ECM, the intracellular levels of reactive oxygen species from both old and young mice were reduced 30-50% compared to those maintained on old-ECM or plastic. We concluded that aging negatively affects the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.

Original languageEnglish (US)
Pages (from-to)1474-1485
Number of pages12
JournalFASEB Journal
Volume25
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Niche
  • Reactive oxygen species
  • Tissue regeneration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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