Mechanical loading modulates intracellular calcium signaling in human mesenchymal stem cells

Mesenchymal stem cells (MSCs) are a promising cell source for tissue-engineered connective tissue repair strategies. Additionally, increasing evidence confirms the role of the mechanical environment in maintaining tissue homeostasis, with calcium signaling implicated as a mediator in mechanotransduction pathways. Spontaneous intracellular calcium signaling was observed in a subset of MSCs embedded within 4% alginate hydrogel constructs, measured by a Ca2+ indicator fluo-4 in conjunction with confocal laser-scanning microscopy. By the use of pair-wise analysis, it was shown that distinct populations of MSCs up-regulated and down-regulated the frequency of calcium transients with the application of a 20% static uniaxial compressive strain of 20 min duration, delivered after a 20 min unstrained period. Calcium transients in control specimens were monitored throughout two unstrained 20 min periods. These values were statistically significant (p<0.05) by chi 2 test of independence. This dual-response indicator highlights the heterogeneous nature of MSC populations, which may have important implications for their successful use in cell therapies.