Y. Sun, W. Li, R. Chen, Z. Lu, J. Ling, Q. Ran, R.L. Jilka, X.-D. Chen

Previously, we reported that in both mouse and human models a native extracellular matrix (ECM) generated by bone marrow cells dramatically promoted mesenchymal stem cell (MSC) proliferation, preserved the stem cell properties, and enhanced their capacity for skeletogenesis (Chen et al, 2007, JBMR, 22:1943; Lai et al, 2010, Stem Cells Dev., 19:1095). This led us to investigate whether culturing aged MSCs on an ECM could improve their number and quality. In particular, we want to take advantage of this established model to address the question of whether there are effects of age on MSC themselves (intrinsic theory), or changes to MSCs by the surrounding ECM (extrinsic theory), or both. A cell-free ECM was prepared from cultured femoral marrow cells from either 3-month old (young) or 18-month 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 impacts the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.

Keywords (Optional): 
Mesenchymal Stem Cells
Extracellular Matrix
Reactive Oxygen Species