36 research outputs found
Combined administration of G-CSF and GM-CSF stimulates monocyte-derived pro-angiogenic cells in patients with acute myocardial infarction
No full textMobilization of endothelial progenitor cells has been suggested to contribute to neo-vascularization of ischemic organs. Aim of this study was to investigate whether the combination of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage (GM)-CSF may influence the expansion of circulating KDR+ cells in patients with acute myocardial infarction (AMI). KDR+ cells significantly increased in peripheral blood of AMI patients treated with G-CSF and GM-CSF compared to untreated patients. This KDR+ cells population was CD14+ but not CD34+ or CD133+. CD14+/KDR+ cells were also obtained in vitro by culturing mononuclear cells from healthy donors in a Rotary Cell Culture System in the presence of G-CSF + GM-CSF, but not of the individual growth factors. CD14+/KDR+ cells, obtained from patients or from in vitro culture, co-expressed hematopoietic (CD45, CD14) and endothelial markers (CD31, CD105, and VE-cadherin). CD14+/KDR+, but not CD14+/KDR- cells, stimulated the organization of human microvascular endothelial cells into capillary-like structures on Matrigel both in vitro and in vivo. The combination of G-CSF and GM-CSF induced a CD14+/KDR+ cell population with potential pro-angiogenic properties
Prospettive e difficoltà della terapia cellulare in Cardiologia: Analisi critica delle sperimentazioni in corso
No full textBackground. Cardiac cell therapy is still restricted to experimental studies and clinical trials. This investigation is an analytic overview of worldwide ongoing trials and is aimed to show useful findings for planning new clinical trials. Methods. Based on the online searching engine of the National Library of Medicine database for clinical trials (www.clinicaltrials.gov), all the ongoing studies registered were analyzed and classified. Results. On May 30, 2009, 95 studies were registered worldwide: 40 of these were conducted in Europe and 4 in Italy. Phase 1, 2, 3 and 4 studies were 28%, 57%, 14% and 1%, respectively; observational and randomized studies were 22% and 78%, respectively. The clinical setting of enrolled patients was acute coronary syndrome in 43 studies (46%), heart failure in 29 studies (30%), chronic heart disease in 23 studies (24%). The treatment strategies investigated are cytokine-induced cell mobilization in 8% and cell implantation in 92%. The cell types used for direct implantation are mononuclear cells in 81%, endothelial precursor cells CD34+ in 11%, endothelial precursor cells CD133 + in 5%, myoblasts in 2% and adipoblasts in 1% of cases. Conclusions. The present snapshot of worldwide ongoing clinical trials provides useful information for planning an experimental clinical program on cardiac cell therapy
Cell Therapy for Refractory Angina: A Reappraisal
No full textCardiac cell-based therapy has emerged as a novel therapeutic option for patients dealing with untreatable refractory angina (RA). However, after more than a decade of controlled studies, no definitive consensus has been reached regarding clinical efficacy. Although positive results in terms of surrogate endpoints have been suggested by early and phase II clinical studies as well as by meta-analyses, the more recent reports lacked the provision of definitive response in terms of hard clinical endpoints. Regrettably, pivotal trials designed to conclusively determine the efficacy of cell-based therapeutics in such a challenging clinical condition are therefore still missing. Considering this, a comprehensive reappraisal of cardiac cell-based therapy role in RA seems warranted and timely, since a number of crucial cell- and patient-related aspects need to be systematically analysed. As an example, the large variability in efficacy endpoint selection appears to be a limiting factor for the advancement of cardiac cell-based therapy in the field. This review will provide an overview of the key elements that may have influenced the results of cell-based trials in the context of RA, focusing in particular on the understanding at which the extent of angina-related endpoints may predict cell-based therapeutic efficacy
Concurrent G-CSF and GM-CSF administration for the induction of bone marrow-derived cell mobilization in patients with acute myocardial infarction: a pilot study evaluating feasibility, safety and efficacy
No full textAIMS:
To verify feasibility and safety of bone marrow stem cells (BMC) mobilization in patients (pts) with acute myocardial infarction (AMI) and to monitor the clinical effects of BMC mobilization in terms of myocardial perfusion and function.
METHODS AND RESULTS:
Eight male pts (median age: 50.5 years) treated with a primary PTCA were enrolled. The mobilization regimen consisted of G-CSF 5 microg/kg/12 h from day 0 to day +2 and GM-CSF 2.5 microg/kg/24 h. All pts underwent coronary angiography, intracoronary doppler flow study, echocardiography, and nuclear thallium scan before treatment and at 6 months. All pts showed increased values of WBC and circulating CD34+ following cytokine administration. No patient died. All patients completed a 6-months follow-up: target lesion revascularization rate was 12,5%, target vessel revascularization rate was 37.5%, angiographic mean ejection fraction increased from 49.8+/-11.9 to 55.4+/-8.7 (p=NS), mean coronary flow reserve from 1.63+/-0.42 to 2.5+/-0.4 (p=0.001), mean Thallium uptake raised from 55.56+/-16.42% to 67.56+/-13.66% (p=0.01), and normally perfused segments from 16% to 52% (p=0.01).
CONCLUSION:
Cytokine-induced BMC mobilization is feasible in AMI pts. Improvements of myocardial perfusion can be expected after PTCA associated with G-CSF and GM-CSF induced mobilization. Further studies are required to define the role of BMC-mobilization and the most effective cytokine combination
The CD133(+) Cell as Advanced Medicinal Product for Myocardial and Limb Ischemia.
No full textIschemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133(+) cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133(+) cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133(+) into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133(+) manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133(+) cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133(+) cell as an anti-ischemic AMP
Outcomes of patients with low-pressure aortic gradient undergoing transcatheter aortic valve implantation: A Meta-analysis
No full textAntiplatelet theRapy after Genous EPC-capturing coroNary stenT implantatiOn: The ARGENTO Study: a prospective, multicenter registry.
No full textBACKGROUND: To investigate the safety and efficacy of Genous Bio-engineered R
stent (GRS) with ≤ 15-day or >15-day dual antiplatelet therapy (DAT), in patients
undergoing percutaneous coronary intervention (PCI), with known or expected low
compliance to long-term DAT (Antiplatelet theRapy after Genous EPC-capturing
coroNary stenT implantatiOn - ARGENTO Study).
METHODS: Consecutive patients without ≤ 12-month revascularization history, known
statins allergy, known hypersensitivity reaction or previous or concomitant
monoclonal and/or recombinant antibodies therapy, treated with single- or
multivessel PCI plus GRS, were prospectively enrolled, at four PCI centers. Major
adverse cardiac events (MACEs), the composite of cardiac death, any myocardial
infarction (MI) and target vessel revascularization (TVR), and stent thrombosis
(ST) cumulative incidences were evaluated.
RESULTS: Between March 2008 and March 2010, 384 patients (70.3% male, 423
lesions) were enrolled. At follow-up (22.8 ± 13.6 months), 8.6% MACEs, 3.4%
cardiac death, 3.4% any MI, 4.7% TVR and 2.3% overall ST (definite/probable ST
1.3%) rates were reported, without differences between ≤ 15-day and >15-day DAT
groups. At Cox multivariable-adjusted regression analysis (Hosmer-Lemeshow
statistic, p=0.50) female sex, diabetes, previous PCI history, <45% left
ventricular ejection fraction at admission and lesion length were identified as
independent MACE predictors. DAT time duration (hazard ratio 1.98; 95% confidence
interval 0.57-6.80, p=0.27) was not independent risk factor for MACEs.
CONCLUSIONS: In consecutive, prospectively enrolled patients with PCI indication
and known or supposed low compliance to long-term DAT, GRS implantation might be
a safe and effective option regardless of DAT duration after stenting (≤ 15 days
or >15 days)
Endothelial Dysfunction Marker Variation in Young Adults with Chronic Apical Periodontitis before and after Endodontic Treatment
No full textIntroduction: Cardiovascular diseases are the leading cause of mortality worldwide. Apical periodontitis (AP) has been associated with an increased risk of cardiovascular diseases. A correlation has been shown between chronic AP and endothelial dysfunction (ED), but there is no evidence to indicate ED improves after endodontic treatment in patients with periapical lesions. The aim of this study was to investigate vascular and molecular markers of early ED before and after root canal treatment in young adults with chronic AP. Methods: Twenty control subjects and 21 patients with AP were assessed at baseline. The AP patients were also evaluated 2 and 12 months post-treatment. Endothelial flow reserve was assessed via an endothelial function test, and enzyme-linked immunosorbent assays were used to evaluate plasma levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor alpha; vasoconstrictor ED marker endothelin (ET)-1; circulating endothelial adhesion markers intercellular adhesion molecule 1 (ICAM-1)/CD54 and soluble vascular cellular adhesion molecule (sVCAM)-1/CD106; soluble CD14; and the endothelial leukocyte adhesion molecule (E-selectin). Results: AP was associated with increased serum levels of ET-1, ICAM-1, E-selectin, IL-1, and sCD14, suggesting early vascular ED, with no macroscopic evidence of a reduction in endothelial flow reserve. Root canal treatment ameliorated inflammation and early ED, lowering plasma levels of IL-1, sCD14, ET-1, ICAM-1/CD54, and E-selectin to those of control subjects. Conclusions: Our findings suggest that AP may drive early vascular ED and that the endodontic therapy of AP ameliorates early ED
Linking cell function with perfusion : insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO)
No full textBackground: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133(+) cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function.
Methods: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133(+) Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction <= 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations.
Results: Patients were treated safely with a mean number of 6.57 +/- 3.45 x 10(6) ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 +/- 8.6 to 13.8 +/- 7.8, p = 0.05) and difference scores (from 12.0 +/- 5.3 to 6.1 +/- 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 +/- 2.2 to 4.0 +/- 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p = 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = -0.79, p = 0.01) and IL-6 (r = -0.76, p = 0.02).
Conclusion: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations
Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: A multicenter observational study
No full textIntroduction: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. Materials and methods: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. Results: 414 hospitalized patients with COVID-19 (66.9 ± 15.0 years, 61.1% male) were included in the present study. During a median follow-up of 28 days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P:.003). Conclusions: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients
