The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133+ stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy.

OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. METHODS: After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133+, CD34+, CD45+ triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. RESULTS: There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). CONCLUSIONS: The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133+ cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function.

Optimization of Mesenchymal Stem Cells to Increase Their Therapeutic Potential.

The heart which has limited renewal and regenerative capacity is a prime target for cellular therapy. Stem cell transplantation has emerged as a promising therapeutic strategy to improve healing of the ischemic heart, repopulate the injured myocardium, and restore cardiac function. However, clinical usefulness is impacted by the quality and quantity of delivered cells, the suboptimal manipulations prior to transplantation, and the general poor viability of the cells transferred particularly to an ischemic microenvironment. Focus is now on developing new ways to enhance stem cell renewal and survival capacity before transplant. This can be done by physical, chemical, pharmacological, or genetic manipulation of cells followed by accurate evaluation of conditioning methods by validated tests.This chapter covers the proper handling of mesenchymal stem cells (human and rat lines) and methodologies to evaluate efficacy and the translational potential of conditioning methods. Specifically, we will cover stem cell culture methods, preconditioning protocols, viability assessment in hypoxic and oxidative challenges as encountered in an ischemic microenvironment, and the proliferative capacity of cells.

HIV incidence in the United States, 1978-1999.

CONTEXT: HIV incidence measurements, which reflect recent or current transmission, are valuable for monitoring the epidemic and evaluating prevention programs. OBJECTIVES: To summarize HIV incidence patterns and trends in U.S. population groups. DATA SOURCES: Publications in English from 1980 through mid-2000. STUDY SELECTION AND STATISTICAL METHODS: We searched the literature for reports of HIV incidence in the United States. Locally weighted scatterplot smoothing was used to generate smooth curves to estimate trends in incidence. Spearman rank correlation was used to estimate the correlation coefficient between prevalence and incidence. DATA SYNTHESIS: In 74 eligible reports, HIV incidence varied widely (0.002-19.8 per 100 person-years [py]) depending on risk group. Among men who have sex with men (MSM), HIV incidence peaked in the early 1980s (5-20/100 py) and then declined but remained high during the 1990s (2-4/100 py). Among injection drug users (IDUs), incidence decreased since the mid-1980s but differed by geographic area; in the 1990s, incidence remained high in the East (1-3/100 py) but was lower in the West (<0.5/100 py). Throughout the late 1980s and 1990s, incidence was low and stable in broader populations (blood donors: <0.01/100 py; military personnel: 0.01-0.07/100 py). The correlation between HIV incidence and prevalence was strong in populations with a prevalence less than 1% (r = 0.94, p<.0001), moderate in populations with a prevalence from 1% to less than 10% (r = 0.57, p<.0001), and weak in populations with a prevalence at least 10% (r = 0.23, p=.09). CONCLUSIONS: HIV prevention in the United States should continue to focus on MSM and IDUs. HIV incidence measurements should be considered for monitoring HIV transmission in MSM, IDUs, and other populations in which seroprevalence is high.