Mobilization of CD34+CXCR4+ Stem/Progenitor Cells and the Parameters of Left Ventricular Function and Remodeling in 1-Year Follow-up of Patients with Acute Myocardial Infarction

Mobilization of stem cells in acute MI might signify the reparatory response. Aim of the Study. Prospective evaluation of correlation between CD34+CXCR4+ cell mobilization and improvement of LVEF and remodeling in patients with acute MI in 1-year followup. Methods. 50 patients with MI, 28 with stable angina (SAP), and 20 individuals with no CAD (CTRL). CD34+CXCR4+ cells, SDF-1, G-CSF, troponin I (TnI) and NT-proBNP were measured on admission and 1 year after MI. Echocardiography and ergospirometry were carried out after 1 year. Results. Number of CD34+CXCR4+ cells in acute MI was significantly higher in comparison with SAP and CTRL, but lower in patients with decreased LVEF ≤40%. In patients who had significant LVEF increase ≥5% in 1 year FU the number of cells in acute MI was significantly higher versus patients with no LVEF improvement. Number of cells was positively correlated (r = 0,41, P = 0,031) with absolute LVEF change and inversely with absolute change of ESD and EDD in 1-year FU. Mobilization of CD34+CXCR4+ cells in acute MI was negatively correlated with maximum TnI and NT-proBNP levels. Conclusion. Mobilization of CD34+CXCR4+ cells in acute MI shows significant positive correlation with improvement of LVEF after 1 year

Myocardial regeneration strategy using Wharton's jelly mesenchymal stem cells as an off-the-shelf "unlimited" therapeutic agent : results from the Acute Myocardial Infarction First-in-Man Study

Introduction: In large-animal acute myocardial infarction (AMI) models, Wharton’s jelly (umbilical cord matrix) mesenchymal stem cells (WJMSCs) effectively promote angiogenesis and drive functional myocardial regeneration. Human data are lacking. Aim: To evaluate the feasibility and safety of a novel myocardial regeneration strategy using human WJMSCs as a unique, allogenic but immuno-privileged, off-the-shelf cellular therapeutic agent. Material and methods: The inclusion criterion was first, large (LVEF ≤ 45%, CK-MB > 100 U/l) AMI with successful infarct-related artery primary percutaneous coronary intervention reperfusion (TIMI ≥ 2). Ten consecutive patients (age 32–65 years, peak hs-troponin T 17.3 ±9.1 ng/ml and peak CK-MB 533 ±89 U/l, sustained echo LVEF reduction to 37.6 ±2.6%, cMRI LVEF 40.3 ±2.7% and infarct size 20.1 ±2.8%) were enrolled. Results: 30 × 106 WJMSCs were administered (LAD/Cx/RCA in 6/3/1) per protocol at ≈ 5–7 days using a cell delivery dedicated, coronary-non-occlusive method. No clinical symptoms or ECG signs of myocardial ischemia occurred. There was no epicardial flow or myocardial perfusion impairment (TIMI-3 in all; cTFC 45 ±8 vs. 44 ±9, p = 0.51), and no patient showed hs-troponin T elevation (0.92 ±0.29 ≤ 24 h before vs. 0.89 ±0.28 ≤ 24 h after; decrease, p = 0.04). One subject experienced, 2 days after cell transfer, a transient temperature rise (38.9°C); this was reactive to paracetamol with no sequel. No other adverse events and no significant arrhythmias (ECG Holter) occurred. Up to 12 months there was one new, non-index territory lethal AMI but no adverse events that might be attributable to WJMSC treatment. Conclusions: This study demonstrated the feasibility and procedural safety of WJMSC use as off-the-shelf cellular therapy in human AMI and suggested further clinical safety of WJMSC cardiac transfer, providing a basis for randomized placebo-controlled endpoint-powered evaluation

Rzeszowski i Krakowski Obszar Metropolitalny

Z wprowadzenia: "Problematyka metropolii i obszaru metropolitalnego od początku XX wieku, (R. Blanchard, N. S. B. Gras) stała się przedmiotem badań i wywodzi się od koncepcji gospodarczej dominacji metropolii oraz teorii regionu miejskiego. „Tkwiące w tych kierunkach [badawczych - ZM] wątki funkcjonalny i morfologiczny zostały powiązane przez R. McKenzie w jego koncepcji społeczności metropolitalnej (metropolitan community), z której powstała teoria obszaru metropolitalnego". Od końca XX wieku problematyka ta okazała się filarem kształtowania się ładu przestrzennego w wielu rozwiniętych krajach. Szczególnie w strukturach przestrzennych krajów europejskich i w Stanach Zjednoczonych metropolie i obszary metropolitalne postrzegane są jako główne centra wzrostu regionalnego, w których skupione zostały wiodące ośrodki wiedzy, nauki, innowacji i kultury. Centra te są motorem rozwoju; mobilizują one pozostałe obszary w kierunku nowoczesnej europejskiej gospodarki opartej na wiedzy. Od rozpoczęcia procesu integracji polskiej gospodarki z nowoczesnymi strukturami zachodnioeuropejskimi, polskie regiony dostosowują się do standardów europejskich. Należy przyjąć, że od ostatniej dekady XX wieku rozpoczął się proces metropolizacji polskiej przestrzeni, a proces ten jest silnie powiązany z praktyką planowania przestrzennego, o czym zdecydował ustawodawca w 2003 r., wprowadzając „przepisy nakazujące sporządzanie planów dla obszarów obejmujących największe miasta Polski wraz z ich bezpośrednim otoczeniem, nazwanych obszarami metropolitalnymi". Awans cywilizacyjny regionów Polski związany jest z rozwojem metropolii i obszarów metropolitalnych. Jak podaje E. Malisiewicz - metropolie są światłami świata, głównymi centrami wiedzy, kreacji i innowacji."(...

Diabetes mellitus and clinical outcomes in carotid artery revascularization using second-generation, MicroNet-covered stents : analysis from the PARADIGM study

INTRODUCTION: Carotid artery stenting (CAS) using conventional (single-layer) stents is associated with worse clinical outcomes in diabetes mellitus (DM) vs. non-DM patients: an effect driven largely by lesion-related adverse events. CAS outcomes with MicroNet-covered stents (MCS) in diabetic patients have not been evaluated. AIM: To compare short- and long-term clinical outcomes and restenosis rate in DM vs. non-DM patients with carotid stenosis treated using MCS. MATERIALS AND METHODS: In a prospective study in all-comer symptomatic and increased-stroke-risk asymptomatic carotid stenosis, 101 consecutive patients (age 51-86 years, 41% diabetics) underwent 106 MCS-CAS. Clinical outcomes and duplex ultrasound velocities were assessed periprocedurally and at 30 days/12 months. RESULTS: Baseline characteristics of DM vs. non-DM patients were similar except for a higher prevalence of recent cerebral symptoms in DM. Type 1 and type 1+2 plaques were more prevalent in DM patients (26.7% vs. 9.8%, p = 0.02; 62.2% vs. 37.7%, p = 0.01). Proximal embolic protection was more prevalent in DM (60% vs. 36%; p = 0.015). 30-day clinical complications were limited to a single periprocedural minor stroke in DM (2.4% vs. 0%, p = 0.22). 12-month in-stent velocities and clinical outcomes were not different (death rate 4.8% vs. 3.3%; p = 0.69; no new strokes). Restenosis rate was not different (0% vs. 1.7%, p = 0.22). CONCLUSIONS: MCS may offset the adverse impact of DM on periprocedural, 30-day, and 12-month clinical complications of CAS and minimize the risk of in-stent restenosis. In this increased-stroke-risk cohort, adverse event rate was low both in DM and non-DM. Further larger-scale clinical datasets including extended follow-ups are warranted