Accumulation of fibronectin in the heart after myocardial infarction: a putative stimulator of adhesion and proliferation of adipose-derived stem cells

Stem cell therapy is a promising treatment after myocardial infarction (MI). A major problem in stem cell therapy, however, is that only a small proportion of stem cells applied to the heart can survive and differentiate into cardiomyocytes. We hypothesized that fibronectin in the heart after MI might positively affect stem cell adhesion and proliferation at the site of injury. Therefore, we investigated the kinetics of attachment and proliferation of adipose-tissue-derived stem cells (ASC) on fibronectin and analysed the time frame and localization of fibronectin accumulation in the human heart after MI. ASCs were seeded onto fibronectin-coated and uncoated culture wells. The numbers of adhering ASC were quantified after various incubation periods (5-30 min) by using DNA quantification assays. The proliferation of ASC was quantified after culturing ASC for various periods (0-9 days) by using DNA assays. Fibronectin accumulation after MI was quantified by immunohistochemical staining of heart sections from 35 patients, after different infarction periods (0-14 days old). We found that ASC attachment and proliferation on fibronectin-coated culture wells was significantly higher than on uncoated wells. Fibronectin deposition was significantly increased from 12 h to 14 days post-infarction, both in the infarction area and in the border-zone, compared with the uninfarcted heart. Our results suggest that a positive effect of fibronectin on stem cells in the heart can only be achieved when stem cell therapy is applied at least 12 h after MI, when the accumulation of fibronectin occurs in the infarcted heart. © 2008 The Author(s)

Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency

Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage

Control of attention by a peripheral visual cue depends on whether the target is difficult to discriminate

The influence of a peripheral cue represented by a gray ring on responsivity to a subsequent target varies. When a vertical line inside a ring was a go target and a white small ring inside a ring was a no-go target, reaction time was shorter at the same location relative to a different location. However, no reaction time difference between the two locations occurred when a white cross inside the ring, instead of the white vertical line inside the ring, was the go target. We investigated whether this last finding was due to a forward masking influence of the cue, a requirement of low attention for the discrimination or a lack of attention mobilization by the cue. In Experiment 1, the intensity of the cue was reduced in an attempt to reduce forward masking. In Experiment 2, the vertical line and the cross were presented in the same block of trials so as to be dealt with a common attentional strategy. In Experiments 3 and 4, the no-go target was a 45º rotated cross inside a ring to increase the difficulty of the discrimination. No evidence was obtained that the cross was forward masked by the cue nor that it demanded less attention to be discriminated from the small ring. There was a facilitation of responsivity by the cue when the small ring was replaced by the rotated cross. The results suggest that when the discrimination to be performed is too easy the cue does not mobilize attention