Abstract
Hyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans. The Radio Electric Asymmetric Conveyer (REAC) technology is aimed to optimize the ions fluxes at the molecular level in order to optimize the molecular mechanisms driving cellular asymmetry and polarization. Here, we show that treatment with 4-methylumbelliferone (4-MU), a potent repressor of type 2 HA synthase and endogenous HA synthesis, dramatically antagonized the ability of REAC to recover the gene and protein expression of Bmi1, Oct4, Sox2, and Nanog in ADhMSCs that had been made senescent by prolonged culture up to the 30th passage. In senescent ADhMSCs, 4-MU also counteracted the REAC ability to rescue the gene expression of TERT, and the associated resumption of telomerase activity. Hence, the anti-senescence action of REAC is largely dependent upon the availability of endogenous HA synthesis. Endogenous HA and HA-binding proteins with REAC technology create an interesting network that acts on the modulation of cell polarity and intracellular environment. This suggests that REAC technology is effective on an intracellular niche level of stem cell regulation.
Highlights
Hyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans
When cells were treated with Radio Electric Asymmetric Conveyer (REAC) in the presence of 4-MU the number of blue stained adipose derived human mesenchymal stem cells (ADhMSCs) was substantially superimposable to the number of SA-β-Gal-positive cells observed in REAC-untreated cells (Fig. 1)
HAS2 plays a pivotal role in preventing cell senescence, acting as a downstream target at which multiple signaling pathways converge to afford growth factor-mediated maintenance of cell differentiation[11,12,13,14]
Summary
Hyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans. Endogenous HA and HA-binding proteins with REAC technology create an interesting network that acts on the modulation of cell polarity and intracellular environment This suggests that REAC technology is effective on an intracellular niche level of stem cell regulation. HA-mediated signaling is essential for the regulation of cell polarization which occurs in response to stimuli that promote non-symmetrical subcellular organization to fulfill functional requirements emerging during migration, adhesion, or mitotic spindle orientation[15,16]. Within this context, we found that treatment of adipose derived human mesenchymal stem cells (ADhMSCs) with REAC technology, was able to invert human stem www.nature.com/scientificreports/. Gaining further insights into the antisenescence effect of REAC may pave the way for future anti-aging approaches in degenerative diseases
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