Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells characterized by their selfrenewal and differentiation potential. Accumulating clinical and preclinical evidence indicate MSCs are a promising cell source for regenerative medical therapies. However, undesirable immortalization, spontaneous transformation, and tumorigenic potential from long-term cultured MSCs have been reported in human and mouse. We report rat MSCs isolated from young donors could undergo transformation in early passage culture. We aimed to characterize the transformed population and determine their therapeutic effects after intracardiac transplantation in the infarcted myocardium. MSCs were isolated from bone marrow of Lewis rats according to standard protocols and cultured under standard conditions. Phenotype of growing cells was assessed by flow cytometry. Following acute myocardial infarction in rats, cells were delivered by intracardiac injection. Cardiac functions were assessed by pressure-volume loops. Infarction size and pathologic effects were evaluated after 6 weeks. The abnormal colonies were detected in culture as early at passage 3. They were noted to appear as distinctly different morphology from typical MSCs, which changed from a normal elongated spindle shape to a compact abnormal morphology. They exhibited rapid cell proliferation. Some subclones lost contact inhibition of cell division and formed multilayer aggregates. Chromosomal instability was detected. They were devoid of surface markers CD29, CD44, CD90, and CD117. Furthermore, there was no significant improvement on infarction size and cardiac function 6 weeks after cell transplantation. Our study highlights the need for establishment of biosafety criteria in regulating cultureexpanded MSCs to achieve the full clinical therapeutic benefits.

Our results suggest that difficulties in suppressing attention towards emotionally laden stimuli might result from deficient executive control in ADHD.

In a number of studies, it has been shown that subjects with attention-deficit/hyperactivity disorder (ADHD) show deficits in executive functioning, i.e. in cognitive functions that subserve planning, monitoring and control of goal-directed behaviour (Martinussen et al., 2005; Willcutt et al., 2005), as well as in emotion regulation (Berlin et al., 2004; Desman et al., 2006). However, no study exists so far examining the interaction between cognition and emotion regulation in subjects with ADHD. In our study, we aimed to examine to what extend arousing emotional picture stimuli may account for differential effects in performance quality in subjects with and without ADHD. Thirty-nine males and females with ADHD aged 18 to 40 years and 40 matched healthy controls performed a working memory n-back task (1-back, 2-back). The task was performed with and without neutral and negative background pictures from the International Affective Picture System (IAPS) which varied in arousal (low, medium, high). Irrespective of ADHD diagnosis, all subjects were slower and demonstrated lower performance accuracy in the 2-back condition compared with the 1-back condition, and all subjects deteriorated with increasing picture arousal. In comparison to healthy controls, subjects with ADHD displayed a deficit in working memory performance in terms of prolonged reaction times and decreased performance accuracy. Beyond this, we found that whereas healthy controls did not display performance deficits until they were presented with high-arousal background pictures, subjects with ADHD were already impaired when presented with medium-arousal background pictures. The implications of these and further findings will be discussed.

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