Effects of the pulsed electromagnetic field PST® on human tendon stem cells: a controlled laboratory study.

BACKGROUND: Current clinical procedures for rotator cuff tears need to be improved, as a high rate of failure is still observed. Therefore, new approaches have been attempted to stimulate self-regeneration, including biophysical stimulation modalities, such as low-frequency pulsed electromagnetic fields, which are alternative and non-invasive methods that seem to produce satisfying therapeutic effects. While little is known about their mechanism of action, it has been speculated that they may act on resident stem cells. Thus, the purpose of this study was to evaluate the effects of a pulsed electromagnetic field (PST®) on human tendon stem cells (hTSCs) in order to elucidate the possible mechanism of the observed therapeutic effects. METHODS: hTSCs from the rotator cuff were isolated from tendon biopsies and cultured in vitro. Then, cells were exposed to a 1-h PST® treatment and compared to control untreated cells in terms of cell morphology, proliferation, viability, migration, and stem cell marker expression. RESULTS: Exposure of hTSCs to PST® did not cause any significant changes in proliferation, viability, migration, and morphology. Instead, while stem cell marker expression significantly decreased in control cells during cell culturing, PST®-treated cells did not have a significant reduction of the same markers. CONCLUSIONS: While PST® did not have significant effects on hTSCs proliferation, the treatment had beneficial effects on stem cell marker expression, as treated cells maintained a higher expression of these markers during culturing. These results support the notion that PST® treatment may increase the patient stem cell regenerative potential.

Association between a school-based intervention and adiposity outcomes in adolescents: The Italian "EAT" project.

OBJECTIVE: To evaluate whether a school-based multicomponent educational program could improve adiposity measures in middle-school adolescents. METHODS: A non-randomized controlled pilot study was conducted in six state middle schools (487 adolescents, 11-15 years) in townships in an urban area around Milan, three schools (n = 262 adolescents) being assigned to the intervention group and three schools (n = 225 adolescents) to the control group. The two-school-year intervention included changes in the school environment (alternative healthy vending machines, educational posters) and individual reinforcement tools (school lessons, textbook, text messages, pedometers, re-usable water bottles). The main outcome measure was change in BMI z-score. The secondary outcomes were changes in waist-to-height ratio (WHtR) and behavioral habits. RESULTS: The intervention was associated with a significant difference in BMI z-score (-0.18 ± 0.03, P<0.01) and in WHtR (-0.04 ± 0.002, P < 0.001), after controlling for baseline covariates. Subgroup analysis showed the maximum association between the intervention and the difference in BMI z-score for girls with overweight/obesity. Physical activity increased and consumption of sugar-sweetened beverages and high-energy snacks decreased in adolescents after the intervention. CONCLUSIONS: A school-based multicomponent intervention conducted at both environmental and individual levels may be effective for reducing adiposity measures mainly in adolescents with overweight/obesity.

Casein phosphopeptides modulate proliferation and apoptosis in HT-29 cell line through their interaction with voltage-operated L-type calcium channels.

At the intestinal level, proliferation and apoptosis are modulated by the extracellular calcium concentration; thus, dietary calcium may exert a chemoprotective role on normal differentiated intestinal cells, while it may behave as a carcinogenesis promoter in transformed cells. Calcium in milk is associated with casein and casein phosphopeptides (CPPs), hence is preserved from precipitation. CPPs were demonstrated to induce uptake of extracellular calcium ions by in vitro intestinal tumor HT-29 cells but only upon differentiation. Here, the hypothesis that CPPs could differently affect proliferation and apoptosis in undifferentiated and differentiated HT-29 cells through their binding with calcium ions was investigated. Results showed that CPPs protect differentiated intestinal cells from calcium overload toxicity and prevent their apoptosis favoring proliferation while inducing apoptosis in undifferentiated tumor cells. The CPP effect on undifferentiated HT-29 cells, similar to that exerted by ethyleneglycol-O, O'-bis(2-aminoethyl)-N, N, N', N'-tetraacetic acid (EGTA), is presumably due to the ability in binding the extracellular calcium. The effect on differentiated HT-29 cells is coupled to the interaction of CPPs with the voltage-operated L-type calcium channels, known to activate calcium entry into the cells under depolarization and to exert a mitogenic effect: the use of an agonist potentiates the cell response to CPPs, while the antagonists abolish the response to CPPs (36% of examined cells) or reduce both the percentage of responsive cells and the increase of intracellular calcium concentration. Taken together, these results confirm the potentialities of CPPs as nutraceuticals/functional food and also as modulators of cellular processes connected to the expression of a cancer phenotype.

Caseinphosphopeptide-induced calcium uptake in human intestinal cell lines HT-29 and Caco2 is correlated to cellular differentiation.

Caseinphosphopeptides (CPPs) are considered as mineral carriers because of their ability to bind and solubilize calcium ions, with the possible role, yet to be definitely assessed, of improving calcium absorption at the intestinal level. Previous works demonstrated that CPPs improve calcium uptake, with increasing intracellular calcium concentration, by human differentiated tumor HT-29 cells, and that this effect correlates with the supramolecular structure of CPPs in the presence of calcium ions. The aim of the present study was to establish whether the CPP effect on calcium uptake is specific for HT-29 cells and depends on the differentiated state of the cells. To this purpose, HT-29 and Caco2 cells, two models of intestinal cells, were differentiated following appropriate protocols, including treatment with 1,25-(OH)2 vitamin D3. The CPP-dependent intracellular calcium rises were monitored at the single-cell level through fura2-fluorescence assays, and cell differentiation was assessed by biochemical and morphological methods. Results clearly showed that the ability to take up extracellular calcium ions under CPP stimulation is exhibited by both HT-29 and Caco2 cells, but only upon cell differentiation. This evidence adds novel support to the notion that CPPs favour calcium absorption, thus possibly acting as cellular bio-modulators and carrying a nutraceutical potential.