A mesenchymal stromal cell gene signature for donor age

PLoS One. 2012;7(8):e42908. doi: 10.1371/journal.pone.0042908. Epub 2012 Aug 23.

Abstract

Human aging is associated with loss of function and regenerative capacity. Human bone marrow derived mesenchymal stromal cells (hMSCs) are involved in tissue regeneration, evidenced by their capacity to differentiate into several lineages and therefore are considered the golden standard for cell-based regeneration therapy. Tissue maintenance and regeneration is dependent on stem cells and declines with age and aging is thought to influence therapeutic efficacy, therefore, more insight in the process of aging of hMSCs is of high interest. We, therefore, hypothesized that hMSCs might reflect signs of aging. In order to find markers for donor age, early passage hMSCs were isolated from bone marrow of 61 donors, with ages varying from 17-84, and clinical parameters, in vitro characteristics and microarray analysis were assessed. Although clinical parameters and in vitro performance did not yield reliable markers for aging since large donor variations were present, genome-wide microarray analysis resulted in a considerable list of genes correlating with human age. By comparing the transcriptional profile of aging in human with the one from rat, we discovered follistatin as a common marker for aging in both species. The gene signature presented here could be a useful tool for drug testing to rejuvenate hMSCs or for the selection of more potent, hMSCs for cell-based therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Animals
  • Cellular Senescence / genetics
  • Female
  • Gene Expression Profiling*
  • Genetic Markers / genetics
  • Genomics
  • Humans
  • Living Donors*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Middle Aged
  • Rats

Substances

  • Genetic Markers

Grant support

This work was supported by The Netherlands Technology Foundation (STW grant TGT.6745) and Senter/Novem research grant (RS, RL, JdB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.