The role of attentional deployment during distancing in adolescents with major depression.

Individuals with major depression (MD) show deficits in cognitive reappraisal. It is yet unexplored how the act of directing visual attention away from/towards emotional aspects impacts on cognitive reappraisal in MD. Thus, we examined the role of attentional deployment during cognitive reappraisal (specifially during distancing) in adolescent MD. 36 MD adolescents and 37 healthy controls (12-18 years) performed a cognitive reappraisal task during which they a) down-regulated self-reported negative affective responses to negative pictures via distancing, or b) simply attended to the pictures. During the task, attentional focus was systematically varied by directing participants' gaze to emotional vs. non-emotional picture aspects. The validity of this experimental manipulation was checked by continuous eye-tracking during the task. Across groups and gaze focus conditions, distancing diminished negative affective responses to the pictures. Regulation success significantly differed between groups dependent on gaze focus: MD adolescents showed relatively less regulation success than controls in the emotional gaze focus condition, while the reverse was true for the non-emotional gaze focus condition. The results suggest that in MD adolescents, an emotional context might interfere with emotion regulatory aims. The findings can provide an important starting point for the development of innovative training regimes that target deficient reappraisal processes in adolescents suffering from MD.

Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.

INTRODUCTION: Cell transplantation for myocardial regeneration has been shown to have beneficial effects on cardiac function after myocardial infarction. Most clinical studies of intramyocardial cell transplantation were performed in combination with coronary artery bypass grafting (CABG). The contribution of implanted stem cells could yet not be clearly distinguished from the effect of the CABG surgery. Our current phase 1 clinical study has focused on the safety and feasibility of CD133+-enriched stem cell transplantation without CABG and its potential beneficial effect on cardiac function. METHOD AND RESULTS: Ten patients with end-stage chronic ischemic cardiomyopathy (ejection fraction <22%) were enrolled in the study. Bone marrow (up to 380 mL) was harvested from the iliac crest. CD133+ cells were purified from bone marrow cells using the CliniMACS device with purities up to 99%. Autologous bone marrow CD133+ cells (1.5-9.7 X 106 cells) were injected into predefined regions. Cardiac functions prior to and 3, 6, and 9 months after cell transplantation were assessed by cardiac magnetic resonance imaging. Stem cell transplantation typically improved the heart function stage from New York Heart Association/Canadian Cardiovascular Society class III-IV to I-II. The mean preoperative and postoperative ventricular ejection fractions were 15.8 +/- 5% and 24.8 +/- 5%, respectively. CONCLUSION: CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy.

We report the case of a 58-year-old man with end-stage non-ischemic cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic function. He underwent autologous CD133+ BM-derived cell transplantation through a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells were injected by the transepimyocardial route. Six months after the operation TTE and cMRI showed a clear improvement in left ventricular contractility.

Umbilical cord blood cell transplantation for myocardial regeneration.

Bone marrow remains the most frequently used source of adult stem cells, but its angiogenic and possibly also myogenic potentials are likely to regress with increasing donor age and morbidity. Recently, cord blood has been suggested as a readily available source for non-embryonic stem cells with high regenerative capacity. We first tested the capacity of mononuclear cells obtained from human umbilical cord blood (UCB(mn)) to migrate to the heart on IV delivery in NOD/Scid mice. As evidenced by the presence of human DNA by PCR analysis, UCB(mn) cells migrated to the heart in 50% of the mice with myocardial infarctions, but in none of the sham-operated control mice. In UCB(mn) cell-positive injured hearts, the infarct size was smaller and capillary density higher in the ischemic myocardium. By immunohistology, we observed endothelial cell differentiation of UCB(mn) cells in the heart but there was no colocalization of UCB cell-specific antibodies with markers of myocyte-type cells. In a second series of experiments, we injected 5 x 10(5) UCB cells enriched for CD133 directly into the necrotic myocardium of NOD/Scid mice. Comparisons were performed with an equivalent number of CD133+ bone marrow (BM) cells or a sham injection in the respective control groups. Both BMCD133+ and UCBCD133+ cells abolished postoperative mortality and improved capillary density in the injured myocardium, but only BMCD133+ cells led to a detectable improvement in myocardial contractility in vivo. We conclude that human UCB cells facilitated neovascularization of ischemic myocardium, but their capacity for formation of contractile neotissue needs further investigation.

A vector based on the SV40 origin of replication and chromosomal S/MARs replicates episomally in CHO cells.

We have developed an episomal replicating expression vector in which the SV40 gene coding for the large T-antigen was replaced by chromosomal scaffold/matrix attached regions. Southern analysis as well as vector rescue experiments in CHO cells and in Escherichia coli demonstrate that the vector replicates episomally in CHO cells. It occurs in a very low copy number in the cells and is stably maintained over more than 100 generations without selection pressure.