Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells

Abstract

The role of cytosolic calcium oscillation has long been recognized in the regulation of cellular and molecular interactions. Information embedded in calcium oscillation can provide molecular cues for cell behavior such as cell differentiation. Although calcium dynamics are versatile and likely to depend on the cell type, the calcium dynamics in human mesenchymal stem cells (hMSCs) and its role in differentiation are yet to be fully elucidated. In the present study we characterized the calcium oscillation profiles in hMSCs before and after subjecting the cells to the osteoinductive factors. Our findings indicate that the calcium spikes decreased rapidly with osteodifferentiation to a level observed in terminally differentiated human osteoblasts. In addition, the calcium oscillations appear to serve as a bidirectional signal during hMSC differentiation. While an altered calcium oscillation pattern may be an indicator for hMSC differentiation, it is also likely to be involved in directing hMSC differentiation. Treatment of hMSCs with a noninvasive electrical stimulation, for example, not only altered the calcium oscillations but also facilitated osteodifferentiation. Regulation of calcium oscillation by external physical stimulation could amplify hMSC differentiation into a tissue-specific lineage and may offer an alternate biotechnology to harness the unique properties of stem cells.

Application of Low-Frequency Alternating Current Electric Fields Via Interdigitated Electrodes: Effects on Cellular Viability, Cytoplasmic Calcium, and Osteogenic Differentiation of Human Adipose-Derived Stem Cells

“…[1][2][3] Within cells and tissues, ionic currents and electric potentials exist naturally and influence cell and tissue function and development. 1,4 Disruption or alteration of ionic gradients or cell surface charges by an applied electric field can lead to changes in cell signaling pathways and gene expression, resulting in differences in differentiation, proliferation, and mobility.…”

“…1,4 Disruption or alteration of ionic gradients or cell surface charges by an applied electric field can lead to changes in cell signaling pathways and gene expression, resulting in differences in differentiation, proliferation, and mobility. [3][4][5] Since the discovery of the natural electrical properties of bone, the idea of coupling endogenous and exogenous electrical activity has been introduced as a possible tool to promote bone fracture healing and differentiation of osteoprogenitor cells. [6][7][8][9][10] Mechanical and electrical stimuli have been known for some time to affect the properties and regenerative capacity of skeletal tissues.…”

Mesenchymal Stem Cells: A Future Option for Intervening Disease Management

“…The threshold of the progenitor cells like MSCs makes it unique in understanding the Ca 2+ homeostasis, for example, human MSCs (hMSCs) exhibit spontaneous Ca 2+ oscillations, a phenomenon not routine in other matured cells and progenitors with a few exceptions [32] though like other cell types in MSCs Ca 2+ oscillations are triggered by influx of extracellular Ca 2+ and release from endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors by calciuminduced calcium release [27]. There are studies that suggest mesenchymal stem cells respond to the extracellular Ca 2+ levels sensed by calcium sensing receptor (CaSR) in the cell membrane for its proliferation and differentiation [33].…”

Mesenchimal stem cells: a possible role in the pathogenesis and treatment of spondyloarthritis

“…Other studies evaluated the optimal conditions for the differentiation of MSCs to tenocytes, chondrocytes, or bone cells The results showed that mesenchymatous cell differentiation toward a tendon or bone phenotype depended on the degree of tensile loading: higher tensile loads promoted osteogenic differentiation (38). Mechanosensitive calcium permeable channels, such as the TRP channel, generate changes in intracellular calcium concentration in response to various mechanical stimuli (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). Activation of these channels at the level of plasma membrane of MSCs would induce intracellular calcium release and confirm the hypothesis that the mechanical tension could also activate MSCs in the pathological process that leads to the development of the SpAs (55-57).…”