Abstract

BackgroundMesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are also prime candidates for regenerative medicine. The contribution of stem cell aging to organismal aging is under debate and one theory is that reparative processes deteriorate as a consequence of stem cell aging and/or decrease in number. Age has been linked with changes in osteogenic and adipogenic potential of MSCs.ResultsHere we report on changes in global gene expression of cultured MSCs isolated from the bone marrow of mice at ages 2, 8, and 26-months. Microarray analyses revealed significant changes in the expression of more than 8000 genes with stage-specific changes of multiple differentiation, cell cycle and growth factor genes. Key markers of adipogenesis including lipoprotein lipase, FABP4, and Itm2a displayed age-dependent declines. Expression of the master cell cycle regulators p53 and p21 and growth factors HGF and VEGF also declined significantly at 26 months. These changes were evident despite multiple cell divisions in vitro after bone marrow isolation.ConclusionsThe results suggest that MSCs are subject to molecular genetic changes during aging that are conserved during passage in culture. These changes may affect the physiological functions and the potential of autologous MSCs for stem cell therapy.

Highlights

  • Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms

  • Mesenchymal stem cells (MSCs) are pluripotent cells that have been reported to reside in virtually all postnatal organs and tissues

  • Characterization of Bone Marrow Mesenchymal Stem Cells In agreement with previous reports [44], early passage cultures were heterogeneous with cells displaying spindle-shaped, flat, and fibroblast-like morphologies (Figure 1(A-C))

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Summary

Introduction

Mesenchymal stem cells (MSC) are pluripotent cells, present in the bone marrow and other tissues that can differentiate into cells of all germ layers and may be involved in tissue maintenance and repair in adult organisms. Because of their plasticity and accessibility these cells are prime candidates for regenerative medicine. Mesenchymal stem cells (MSCs) are pluripotent cells that have been reported to reside in virtually all postnatal organs and tissues (reviewed in [1,2,3]) They are defined by their ability to adhere to plastic, to differentiate into bone, cartilage and fat, and by expression of specific sets of cell-surface markers. Mouse MSCs migrate to multiple tissues and differentiate into

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