Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/PI3K pathway

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch-wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase-2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch-wound healing in a concentration-dependent manner. The HGF receptor, c-Met, was rapidly phosphorylated in the nemosis-stimulated keratinocytes. Nemosis-induced in vitro scratch-wound healing was inhibited by an HGF-neutralizing antibody as well as the small molecule c-Met inhibitor, SU11274. HGF-induced in vitro scratch-wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen-activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF-induced keratinocyte in vitro scratch-wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch-wound healing, and that in this effect signaling via HGF/c-Met is involved.     

Neural network adapted to wound cell analysis in surgical patients

Assessment of the real state of wound healing of closed surgical wounds is uncertain both clinically and from conventional laboratory tests. Therefore, a novel approach based on early analysis of exactly timed wound cells, computerized further with an artificial neural network, was developed. At the end of routine surgery performed on 481 children under 18 years of age, a specific wound drain Cellstick^? was inserted subcutaneously between the wound edges to harvest wound cells. The Cellsticks^? were removed from 1 to 50 hours, mainly at hour 3 or 24 postsurgery. Immediately, the cellular contents were washed out using a pump constructed for the purpose. After cytocentrifugation, the cells were stained and counted differentially. Based on their relative proportions at selected time intervals, an artificial self‐organizing neural map was developed. This was further transformed to a unidirectional linear graph where each node represents one set of relative cell quantities. As early as 3 hours, but more precisely 24 hours after surgery, the location of the nodes on this graph showed individually the patients' initial speed of wound inflammatory cell response. Similarly, timed Cellstick^? specimens from new surgical patients could be analyzed, computerized, and compared with these node values to assess their initial speed in wound inflammatory cell response. Location of the node on the graph does not express the time lapse after surgery but the speed of wound inflammatory cell response in relation to that of other patients.     

Role of angiogenic growth factors in transplant coronary artery disease

Transplant coronary artery disease (TxCAD) as a manifestation of chronic rejection is a major limitation to long‐term survival of heart transplant recipients. Although the exact molecular and cellular mechanisms contributing to neointimal formation are unknown, it has been generally believed that smooth muscle cells (SMC) of donor origin migrate from the media into the subendothelial layer of the vascular wall, where SMC proliferate and synthesize extracellular matrix resulting in intimal thickening. However, recent observations indicate that hematopoietic and vascular progenitor cells derived from recipient bone marrow may contribute to the arteriosclerotic lesion formation in the coronary arteries of the transplant. On the other hand, studies on postnatal hematopoiesis indicate that angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin‐1 (Ang1) may regulate the recruitment of these cells into distant organs. Furthermore, embryonic VEGFR‐2 ⁺ /CD34 ⁺ stem cells may serve as vascular progenitor cells and their differentiation into endothelial cells and SMC may be regulated by VEGF and platelet‐derived growth factor (PDGF), respectively. In this review, we discuss the role of angiogenic growth factors such as VEGF, Ang, and PDGF in the recruitment of hematopoietic and vascular progenitor cells in TxCAD and suggest novel therapies targeted at homing, differentiation and proliferation of these cells in the allograft.     

The reflection of retinal light response information onto the superior colliculus in the rat

Background The functional principles of mediation of retina-encoded visual information through the optic nerve to the superior colliculus (SC) of the contralateral brain hemisphere were investigated in non-drugged and unrestrained albino rats by considering the following issues: (1) the type of information transmitted, (2) the response components of the retina and SC involved in encoding the transmitted information, and (3) the timing of related processes. Methods The field potential responses for different intensities of flashes, under different background illuminations, were simultaneously recorded from the sclera area of the eye and the optic layer of the contralateral SC. Results It was found that the b-wave crest of the retinal electroretinogram (ERG) and the peak-1 or peak-2 of the SC correlate by their amplitude, while the a-wave trough of the retinal ERG and the peak-1 of the SC correlate by their latency. The values of these mutually correlating response components were invariably determined by the given light response bias of the retina (photoreceptors), the change in the photon flux of the light stimulus and, obviously, the change in the wavelength of the light stimulus. The a-wave trough, peak-1, b-wave crest and peak-2 were invariably induced in this time-order. Conclusions The data suggest that the information properties of (a) intensity, (b) presentation time and, obviously, (c) colour of the light stimulus, such as are shed on the retina, and information about the light response bias of the retina are mediated correlatively and quantitatively to the cell network system of the SC through the optic nerve. These processes must happen during the a-to-b-wave phases of the ERG. The data indicate that the random-type variations in the activity of the related cellular systems may actually be harnessed in mediating the defined information properties of the visual stimulus from the retina to the SC of the brain through the optic nerve. This study shows a method of measuring the function of the optic nerve. Results of this study have tentatively been presented at the ARVO 2004 meeting. The author has full control of all primary data and agrees to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review this data if requested.     

Low serum selenium concentration in patients with cervical or endometrial cancer

Serum concentrations of selenium were determined in 37 patients with cervical and 64 patients with endometrial cancer. The patients had lower (P less than 0.001) serum concentrations of selenium than the age-, weight- and place of residence-matched paired control women. There was no difference in the selenium concentration between various age groups or different clinical stages of cervical or endometrial cancer. A low serum concentration of selenium might be a contributing factor in uterine carcinogenesis.     

Noise frame duration,masking potency and whiteness of temporal noise

PURPOSE: Because of the limited contrast range, increasing the duration of the noise frame is often the only option for increasing the masking potency of external, white temporal noise. This, however, reduces the high-frequency cutoff beyond which noise is no longer white. This study was conducted to determine the longest noise frame duration that produces the strongest masking effect and still mimics white noise on the detection of sinusoidal flicker. METHODS: Contrast energy thresholds (E(th)) were measured for flicker at 1.25 to 20 Hz in strong, purely temporal (spatially uniform), additive, external noise. The masking power of white external noise, characterized by its spectral density at zero frequency N0, increases with the duration of the noise frame. RESULTS: For short noise frame durations, E(th) increased in direct proportion to N0, keeping the nominal signal-to-noise ratio [SNR = (E(th)/N0)(0.5)] constant at threshold. The masking effect thus increased with the duration of the noise frame and the noise mimicked white noise. When noise frame duration and N0 increased further, the nominal SNR at threshold started to decrease, indicating that noise no longer mimicked white noise. The minimum number of noise frames per flicker cycle needed to mimic white noise decreased with increasing flicker frequency from 8.3 at 1.25 Hz to 1.6 at 20 Hz. CONCLUSIONS: The critical high-frequency cutoff of detection-limiting temporal noise in terms of noise frames per signal cycle depends on the temporal frequency of the signal. This is opposite to the situation in the spatial domain and must be taken into consideration when temporal signals are masked with temporal noise.