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

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.

Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem Cells on Three-Dimensional Scaffolds

“…[23][24][25]28,37 To further mimic an in vivo situation, we took this technology to the next level by developing a 3D tissue-specific scaffold and investigated its effect on the proliferation and differentiation capacity of MSCs. Such 3D scaffolds coated with a native ECM synthesized by bone marrow stromal cells exhibited a biomimetic bonemarrow-like microenvironment (or ''niche'') in vitro.…”

“…[25][26][27][28] To further mimic an in vivo situation, a 3D stem cell culture system that represents the physiological architecture of the bone marrow tissue may offer new insights on MSC function. Researchers utilize a variety of scaffolds to study the behavior of MSCs in 3D cultures.…”

Adipose-Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential

“…Most of the data regarding ADSC regenerative potential were obtained from cells delivered from relatively healthy young donors; however, it was known that aging and disease itself may negatively affect MSC activities [21][22][23][24][25][26], including proliferation and differentiation potential [27][28][29][30] as well as angiogenic properties [29,31]. Because MSCs are considered to be components of the vessel wall and take part in its reparation after injury, their cellular modification due to aging can be an important pathogenic factor of agerelated diseases such as atherosclerosis, diabetes, and arterial hypertension [32].…”

Approaches for Stimulating Proliferation of Stem Cells in Vitro

“…Moreover, it has been demonstrated that certain culture conditions, including the use of specific atmospheric conditions and culture substrates, exert positive effects on not only the proliferation rate, but also the extent of proliferation. For instance, low oxygen condition, suitable extracellular matrix (ECM), small molecules compounds have been applied to stimulate the proliferation of stem cells in vitro [19][20][21]. Low oxygen condition largely mimics normal physiological condition of tissues.…”