Intravenous Followed by X-ray Fused with MRI-Guided Transendocardial Mesenchymal Stem Cell Injection Improves Contractility Reserve in a Swine Model of Myocardial Infarction.

The aim of this study is to determine the effects of early intravenous (IV) infusion later followed by transendocardial (TE) injection of allogeneic mesenchymal stem cells (MSCs) following myocardial infarction (MI). Twenty-four swine underwent balloon occlusion reperfusion MI and were randomized into 4 groups: IV MSC (or placebo) infusion (post-MI day 2) and TE MSC (or placebo) injection targeting the infarct border with 2D X-ray fluoroscopy fused to 3D magnetic resonance (XFM) co-registration (post-MI day 14). Continuous ECG recording, MRI, and invasive pressure-volume analyses were performed. IV MSC plus TE MSC treated group was superior to other groups for contractility reserve (p = 0.02) and freedom from VT (p = 0.03) but had more lymphocytic foci localized to the peri-infarct region (p = 0.002). No differences were observed in post-MI remodeling parameters. IV followed by XFM targeted TE MSC therapy improves contractility reserve and suppresses VT but does not affect post-MI remodeling and may cause an immune response.

Bilateral administration of autologous CD133+ cells in ambulatory patients with refractory critical limb ischemia: lessons learned from a pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND AIMS: CD133+ cells confer angiogenic potential and may be beneficial for the treatment of critical limb ischemia (CLI). However, patient selection, blinding methods and end points for clinical trials are challenging. We hypothesized that bilateral intramuscular administration of cytokine-mobilized CD133+ cells in ambulatory patients with refractory CLI would be feasible and safe. METHODS: In this double-blind, randomized sham-controlled trial, subjects received subcutaneous injections of granulocyte colony-stimulating factor (10 µg/kg per day) for 5 days, followed by leukapheresis, and intramuscular administration of 50-400 million sorted CD133+ cells delivered into both legs. Control subjects received normal saline injections, sham leukapheresis and intramuscular injection of placebo buffered solution. Subjects were followed for 1 year. An aliquot of CD133+ cells was collected from each subject to test for genes associated with cell senescence. RESULTS: Seventy subjects were screened, of whom 10 were eligible. Subject enrollment was suspended because of a high rate of mobilization failure in subjects randomly assigned to treatment. Of 10 subjects enrolled (7 randomly assigned to treatment, 3 randomly assigned to control), there were no differences in serious adverse events at 12 months, and blinding was preserved. There were non-significant trends toward improved amputation-free survival, 6-minute walk distance, walking impairment questionnaire and quality of life in subjects randomly assigned to treatment. Successful CD133+ mobilizers expressed fewer senescence-associated genes compared with poor mobilizers. CONCLUSIONS: Bilateral administration of autologous CD133+ cells in ambulatory CLI subjects was safe, and blinding was preserved. However, poor mobilization efficiency combined with high CD133+ senescence suggests futility in this approach.

Psychiatric disorders in smokers seeking treatment for tobacco dependence: relations with tobacco dependence and cessation.

OBJECTIVE: The present research examined the relation of psychiatric disorders to tobacco dependence and cessation outcomes. METHOD: Data were collected from 1,504 smokers (58.2% women; 83.9% White; mean age = 44.67 years, SD = 11.08) making an aided smoking cessation attempt as part of a clinical trial. Psychiatric diagnoses were determined with the Composite International Diagnostic Interview structured clinical interview. Tobacco dependence was assessed with the Fagerström Test of Nicotine Dependence (FTND) and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). RESULTS: Diagnostic groups included those who were never diagnosed, those who had ever been diagnosed (at any time, including in the past year), and those with past-year diagnoses (with or without prior diagnosis). Some diagnostic groups had lower follow-up abstinence rates than did the never diagnosed group (ps < .05). At 8 weeks after quitting, strong associations were found between cessation outcome and both past-year mood disorder and ever diagnosed anxiety disorder. At 6 months after quitting, those ever diagnosed with an anxiety disorder (OR = .72, p = .02) and those ever diagnosed with more than one psychiatric diagnosis (OR = .74, p = .03) had lower abstinence rates. The diagnostic categories did not differ in smoking heaviness or the FTND, but they did differ in dependence motives assessed with the WISDM. CONCLUSION: Information on recent or lifetime psychiatric disorders may help clinicians gauge relapse risk and may suggest dependence motives that are particularly relevant to affected patients. These findings also illustrate the importance of using multidimensional tobacco dependence assessments.