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1.
Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients.
Dantas, JR, Araújo, DB, Silva, KR, Souto, DL, de Fátima Carvalho Pereira, M, Luiz, RR, Dos Santos Mantuano, M, Claudio-da-Silva, C, Gabbay, MAL, Dib, SA, et al
Archives of endocrinology and metabolism. 2021;(3):342-351
Abstract
OBJECTIVE Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. METHODS In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 × 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). RESULTS In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. CONCLUSION Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.
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Mediterranean, but not lacto-ovo-vegetarian, diet positively influence circulating progenitor cells for cardiovascular prevention: The CARDIVEG study.
Cesari, F, Dinu, M, Pagliai, G, Rogolino, A, Giusti, B, Gori, AM, Casini, A, Marcucci, R, Sofi, F
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(6):604-610
Abstract
AIM: To evaluate the possible association between dietary habits and progenitor cells using data obtained from a randomized crossover trial using two different diets, lacto-ovo-vegetarian (VD) and Mediterranean (MD), the CARDIVEG study. METHODS AND RESULTS Eighty clinically healthy subjects with a low-to-moderate cardiovascular risk profile (61 F; 19 M; mean age: 50.7 ± 11.6 years) were randomly assigned to isocaloric VD and MD diets lasting three months each, and then crossed. The two diets showed no effects on endothelial progenitor cells and circulating endothelial cells but opposite effects on circulating progenitor cells. In fact, VD determined significant (p < 0.05) and negative changes on circulating progenitor cells, with an average geometric variation of -130 cells/106 events for CD34+/CD45-/dim, -80 cells/106 events for CD133+/CD45-/dim, and -84 cells/106 events for CD34+/CD133+/CD45-/dim while MD determined significant (p < 0.05) and positive changes for CD34+/CD45-/dim levels, with a geometric mean increase of +54 cells/106 events. No significant correlations were observed between changes in progenitor cells and changes in inflammatory parameters during the VD phase. On the other hand, during the MD phase negative correlations between changes of CD34+/CD45-/dim and interleukin-6 (R = -0.324; p = 0.004) as well as interleukin-8 (R = -0.228; p = 0.04) and monocyte chemotactic protein-1 (R = -0.277; p = 0.01), were observed. These correlations remained significant also after adjustment for confounding factors only for CD34+/CD45-/dim and interleukin-6 (β = -0.282; p = 0.018) and monocyte chemotactic protein-1 (β = -0.254; p = 0.031). CONCLUSIONS MD, but not VD, reported a significant and positive effect on circulating progenitor cells in a group of subjects at low-to-moderate cardiovascular risk, probably acting through the modulation of inflammatory parameters.
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Adjunctive laser-stimulated stem-cells therapy to primary reperfusion in acute myocardial infarction in humans: Safety and feasibility study.
Elbaz-Greener, G, Sud, M, Tzuman, O, Leitman, M, Vered, Z, Ben-Dov, N, Oron, U, Blatt, A
Journal of interventional cardiology. 2018;(6):711-716
Abstract
BACKGROUND Low-level laser therapy (LLLT) has photobiostimulatory effects on stem cells and may offer cardioprotection. This cell-based therapy may compliment primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVE In this randomized control trial, our primary objective was to determine the safety and feasibility of LLLT application to the bone marrow in patients with STEMI undergoing PPCI. METHODS We randomly assigned patients undergoing PPCI to LLLT or non-laser therapy (NLT). In the LLLT group, 100 s of laser therapy was applied to the tibia bone prior to PPCI, as well as 24 and 72 h post-PPCI. In the control group, the power source was turned off. The primary outcome was the difference in door-to-balloon (D2B) time, and additional outcomes included differences in circulating cell counts, cardiac enzymes, and left-ventricular ejection fraction (LVEF) at pre-specified intervals post-PPCI. RESULTS Twenty-four patients were randomized to LLLT (N = 12) or NLT (N = 12). No adverse effects of the treatment were detected. The D2B time was not significantly different between the groups (41 ± 8 vs 48 ± 1 min; P = 0.73). Creatinine Phosphokinase area under the curve, was lower after LLLT (22 ± 10) compared to NLT (49 ± 12), but this was not statistically significant (P = 0.08). Troponin-T was significantly lower after LLLT (2.7 ± 1.4 ng/mL) in comparison to NLT (5.2 ± 1.8 ng/mL. P < 0.05). At 9 months, LVEF improved in both groups without a significant difference between LLLT (55 ± 9%) and NLT (52 ± 9%; P = 0.90). CONCLUSION LLLT is a safe and feasible adjunctive cell-based therapy to PPCI that may benefit ischemic myocardium.
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Alp Rose stem cells, olive oil squalene and a natural alkyl polyglucoside emulsifier: Are they appropriate ingredients of skin moisturizers - in vivo efficacy on normal and sodium lauryl sulfate - irritated skin?
Filipović, M, Gledović, A, Lukić, M, Tasić-Kostov, M, Isailović, T, Pantelić, I, Vuleta, G, Savić, S
Vojnosanitetski pregled. 2016;(11):991-1002
Abstract
BACKGROUND/AIM: Since skin moisturization may be achieved by both actives and chosen carrier, plant stem cells, squalene and natural alkyl polyglucoside emulsifier may be potential components of contemporary cosmetic products. The aim of the study was in vivo evaluation of the skin irritation potential and the efficacy of Alpine Rose stem cells incorporated into li-posomes and olive oil squalene as ingredients of moisturizing creams, with respect to the novel emulsifier used for creams’ stabilization. METHODS With the employment of noninvasive skin biophysical measurements, skin hydration (EC), transepi-dermal water loss (TEWL), erythema index (EI) and viscoelas-ticity were measured on 76 healthy volunteers. In the first phase, skin irritation after a 24-hour occlusion and the long-term efficacy of creams (a 21-day study) on healthy skin were evaluated. Phase II of the study focused on the cream efficacy assessment after a 6-day treatment of sodium lauryl sulfate-irritated skin. RESULTS After a 24-hour occlusion, there were no significant changes in the EI for any tested sample. In the second phase of the study, the EI was not significantly altered for the cream containing squalene, while the application of all active samples resulted in a significant reduction of TEWL. In both phases of the study an EC increase was recorded, espe-cially for the squalene-containing cream. CONCLUSION Due to the lack of skin irritation and skin barrier impairment along with the marked hydration effect, it could be said that the in-vestigated actives incorporated into alkyl polyglucoside emulsi-fier-stabilized creams may be safely applied as ingredients for "tailor-made" cosmetic moisturizers intended for normal and dry skin care, whereas olive oil squalene could be used for the treatment of irritated or sensitive skin as well. [Projekat Ministarstva nauke Republike Srbije, br. TR34031]
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Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.
Grassi, D, Draijer, R, Schalkwijk, C, Desideri, G, D'Angeli, A, Francavilla, S, Mulder, T, Ferri, C
Nutrients. 2016;(11)
Abstract
(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.
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Peri-procedural tight glycemic control during early percutaneous coronary intervention up-regulates endothelial progenitor cell level and differentiation during acute ST-elevation myocardial infarction: effects on myocardial salvage.
Marfella, R, Rizzo, MR, Siniscalchi, M, Paolisso, P, Barbieri, M, Sardu, C, Savinelli, A, Angelico, N, Del Gaudio, S, Esposito, N, et al
International journal of cardiology. 2013;(4):3954-62
Abstract
BACKGROUND We examined the effects of peri-procedural intensive glycemic control during early percutaneous coronary intervention (PCI) on the number and differentiation of endothelial progenitor cells (EPCs) and myocardial salvage (MS) in hyperglycemic patients with first ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS We conducted a randomized, prospective, open label study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients (glucose ≥140 mg/dl) were randomized to intensive glycemic control (IGC) for almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary end point of the study was salvage index, measured as the proportion of initial perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7 days after STEMI) and myocardium salvaged by therapy (6 months after STEMI). Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1 levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean plasma glucose during peri-procedural period was greater in CGC group than in IGC group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1 levels were significantly higher in IGC group than in CGC, peaking after 24 h (P < 0.01). In the IGC group, the salvage index was greater than in patients treated with CGC (P < 0.001). CONCLUSIONS Optimal peri-procedural glycemic control, by increasing EPC number and their capability to differentiate, may improve the myocardial salvage.
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Effect of 40 mg versus 10 mg of atorvastatin on oxidized low-density lipoprotein, high-sensitivity C-reactive protein, circulating endothelial-derived microparticles, and endothelial progenitor cells in patients with ischemic cardiomyopathy.
Huang, B, Cheng, Y, Xie, Q, Lin, G, Wu, Y, Feng, Y, Gao, J, Xu, D
Clinical cardiology. 2012;(2):125-30
Abstract
BACKGROUND There are few recent data to delineate the beyond lipids-decreased effect of statins and the effect of different doses of statins on endothelial-derived microparticles (EMPs) and circulating endothelial progenitor cells (EPCs) in patients with ischemic cardiomyopathy (ICM). HYPOTHESIS Statins might have the beyond lipids-decreased effect and there were different effects between different doses of statins on EMPs and circulating EPCs in patients with ICM. METHODS One hundred patients with ICM and 100 healthy examined people, who served as the normal control group, were recruited to this study. Patients were randomly divided into 2 groups: 10-mg atorvastatin group (n = 50) and 40-mg atorvastatin group (n = 50). All subjects were followed for 1 year. The levels of serum lipids, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein (hsCRP), circulating EPCs, and EMPs were examined in all subjects. The incidences of adverse reactions in the 2 study groups were determined. RESULTS At the beginning of this study, there were no significant differences in baseline characteristics between the 2 study groups. At the end of this study, the levels of total cholesterol, low-density lipoprotein, serum hsCRP, oxLDL, and circulating EMPs were significantly decreased; circulating EPCs were significantly increased in the 40-mg atorvastatin group compared to the 10-mg atorvastatin group, P < 0.05. The multivariate linear regression analysis indicated that receiving only 40 mg of atorvastatin had a significant effect on the levels of circulating EPCs (β = 0.252,P = 0.014). There were no significant differences in the adverse reactions between the 2 groups. CONCLUSIONS Use of 40 mg of atorvastatin might decrease the levels of circulating EMPs and increase the number of circulating EPCs in patients with ICM in comparison with 10 mg of atorvastatin, and the effect might be independent of the decrease of lipids, oxLDL, and hsCRP.
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Effect of antihypertensive treatment on circulating endothelial progenitor cells in patients with mild essential hypertension.
de Ciuceis, C, Pilu, A, Rizzoni, D, Porteri, E, Muiesan, ML, Salvetti, M, Paini, A, Belotti, E, Zani, F, Boari, GE, et al
Blood pressure. 2011;(2):77-83
Abstract
It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.
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Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium.
Marin, C, Ramirez, R, Delgado-Lista, J, Yubero-Serrano, EM, Perez-Martinez, P, Carracedo, J, Garcia-Rios, A, Rodriguez, F, Gutierrez-Mariscal, FM, Gomez, P, et al
The American journal of clinical nutrition. 2011;(2):267-74
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Abstract
BACKGROUND Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Activation or injury of the endothelium leads to a variety of inflammatory disorders, including the release of microparticles. Endothelial progenitor cells may contribute to the maintenance of the endothelium by replacing injured mature endothelial cells. OBJECTIVE We studied the influence of dietary fat on the release of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) in elderly subjects. DESIGN Twenty healthy, elderly subjects (10 men and 10 women) consumed 3 diets following a randomized crossover design, each for 4 wk: a saturated fatty acid diet; a low-fat, high-carbohydrate diet; and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acids. We investigated total microparticles, EMPs from activated endothelial cells (activated EMPs), EMPs from apoptotic endothelial cells (apoptotic EMPs), EPCs, oxidative stress variables, and ischemic reactive hyperemia (IRH). RESULTS The MedDiet led to lower total microparticle, activated EMP, and apoptotic EMP concentrations and higher EPC numbers than did the other diets (P < 0.001). We detected lower superoxide dismutase activity (P < 0.001), a higher plasma β-carotene concentration (P < 0.001), and lower urinary isoprostane and plasma nitrotyrosine concentrations after consumption of the MedDiet than after consumption of the other 2 diets (P < 0.05). Furthermore, the occurrence of IRH was higher after consumption of the MedDiet than after consumption of the other 2 diets (P < 0.05). CONCLUSION Consumption of the MedDiet induces a reduction in endothelial damage and dysfunction, which is associated with an improvement in the regenerative capacity of the endothelium, in comparison with 2 other diets.
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Randomized comparison of endothelial progenitor cells capture stent versus cobalt-chromium stent for treatment of ST-elevation myocardial infarction. Six-month clinical, angiographic, and IVUS follow-up.
Bystroň, M, Cervinka, P, Spaček, R, Kvašňák, M, Jakabčin, J, Cervinková, M, Kala, P, Widimský, P
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2010;(5):627-31
Abstract
PURPOSE The aim of this trial was to assess the feasibility and safety of endothelial progenitor cells capture (EPC) stent in the treatment of acute ST-elevation myocardial infarction (STEMI) when compared with cobalt-chromium stents (CoCr). METHODS Between July 2006 and May 2008, 100 patients with single vessel disease undergoing primary PCI for STEMI were randomly assigned to receive either EPC stent (N = 50) or CoCr stent (N = 50). High-pressure stent implantation was carried out in both groups. Dual antiplatelet treatment was administered for 30 days in both groups. All patients underwent 6-month clinical, angiographic, and IVUS follow-up. RESULTS The rate of major adverse cardiovascular events (MACEs) at 30 days was comparable in both groups. At 6-month follow-up, the rates of MACEs and TLR in the EPC stent group when compared with CoCr stent were 24% vs.10%; P = 0.06 and 14% vs. 4%; P = 0.08, respectively. There were three cases (6%) of stent thrombosis (ST) in the EPC stent group versus none in CoCr group. CONCLUSION The use of EPC capture stents in the setting of STEMI is feasible and safe in terms of 30-days outcome. However, at the 6-month follow-up, we found a trend of higher rates of MACE and TLR in the EPC stent capture group compared to CoCr stents. The study does not support the use of EPC capture stents with short duration dual antiplatelet therapy in patients with STEMI. Future randomized studies with large sample sizes would be necessary to demonstrate the safety of such approach. © 2010 Wiley-Liss, Inc.