1,721,081 research outputs found

    Skin Stem Cells in Cancer

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    Stem cells (SCs) are responsible for maintaining and regenerating tissues and show unique defining characteristics, including self-renewal, asymmetrical cell division, low proliferation rate, and clonogenic potential. Niches of epidermal SCs have been identified in the bulge of hair follicles, the basal layer of the interfollicular epidermis, and the base of sebaceous glands. Accumulating evidence suggests that multipotent bulge cells generate hair follicles under physiological conditions and regenerate the epidermis and sebaceous glands in response to skin injury. In contrast, SCs of the interfollicular epidermis and sebaceous glands are lineage specific and generate their respective tissues without recruiting SCs from the bulge compartment. Cancer stem cells (CSCs) represent a class of tumor cells exhibiting stem cell-like properties and ability to initiate tumors. They are derived from SCs or from non-stem cells that acquire self-renewal potential. Likely SCs, CSCs express regulatory factors of self-renewal, such as SOX2, MYC, and OCT4, and some common “stemness” pathways, such as Wnt signaling. In contrast, they could not be multipotent and lead to single lineage tumors, such as squamous cell carcinoma (SCC) (epidermal lineage), various follicular tumor types (hair follicle lineage), and sebaceous gland tumors (sebaceous lineage). Currently, several studies on CSC biology have been performed to develop new targeted therapies for patients with skin tumors with poor prognoses

    Micropatterned three-dimensional hydrogel system to study human endothelial - mesenchymal stem cell interactions

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    The creation of vascularized engineered tissues of clinically relevant size is a major challenge of tissue engineering. While it is known that endothelial and mural vascular cells are integral to the formation of stable blood vessels, the specific cell types and optimal conditions for engineered vascular networks are poorly understood. To this end, we investigated the vasculogenic potential of human mesenchymal stem cell (MSC) populations derived from three different sources: (a) bone marrow aspirates; (b) perivascular cells from the umbilical cord vein; and (c) perivascular cells from the umbilical cord artery. Cell populations were isolated and identified as MSCs according to their phenotypes and differentiation potential. Human umbilical vein endothelial cells (HUVECs) were used as a standard for endothelial cells. A novel co-culture system was developed to study cell cell interactions in a spatially controlled three-dimensional (3D) fibrin hydrogel model. Using microfluidic patterning, it was possible to localize hydrogel-encapsulated HUVECs and MSCs within separate channels spaced at 500, 1000 or 2000 mu m. All three MSC populations had similar expression profiles of mesenchymal cell markers and similar capacity for osteogenic and adipogenic differentiation. However, bone marrow-derived MSCs (but not umbilical vein or artery derived MSCs) showed strong distance-dependent migration toward HUVECs and supported the formation of stable vascular networks resembling capillary-like vasculature. The presented approach provides a simple and robust model to study the cell cell communication of relevance to engineering vascularized tissues

    Expression of the beacon gene in the rat adrenal gland: direct inhibitory effect of beacon[47-73] on aldosterone secretion from dispersed adrenal zona glomerulosa cells

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    Beacon gene was recently identified in the rat hypothalamus, and there is evidence that beacon may be involved in the functional regulation of neuroendocrine axes. Reverse transcription-polymerase chain reaction and immunocytochemistry showed the expression of beacon mRNA and protein in the rat adrenal gland, especially in the cortex. Beacon[47-73], at a concentration over 10(-7) M decreased basal aldosterone secretion from dispersed rat zona glomerulosa (ZG) cells, without affecting the ACTH-stimulated one. Basal and agonist-stimulated corticosterone secretion from dispersed zona fasciculata-reticularis cells and catecholamine release from adrenomedullary slices were unaffected by beacon[47-73]. The suppressive effect of beacon[47-73] on aldosterone secretion from ZG cells was abolished by either H-89 or calphostin-C, which are inhibitors of protein kinase A and C signaling cascades. Taken together, these findings allow us to suggest that beacon can be included in the group of regulatory peptides involved in the fine tuning of ZG secretory activity

    Expression of the beacon gene in endocrine glands of the rat

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    Beacon gene has been recently identified in the rat hypothalamus, and reported to be overexpressed in obese animals. This pattern of expression suggests that beacon may be involved in the functional regulation of neuroendocrine axes. Hence, we have investigated the expression of beacon in the endocrine system of the rat. Reverse transcription-polymerase chain reaction showed the expression of beacon mRNA in the hypothalamus, adenohypophysis, thyroid gland, adrenal gland, testis, ovary and pancreatic islets. Immunocytochemistry demonstrated the presence of the beacon immunoreactivity in all tissues studied, the staining being very intense in the neurons of paraventricular and supraoptic nuclei, the basophils of adenohypophysis, the parathyroid gland, adrenocortical cells, testis Leydig cells, ovary thecal, granulosa and lutein cells, and pancreatic islets. Due the fact that beacon has been included in the ubiquitin-like protein family, its widespread expression in rat endocrine tissues is not astonishing. The in vivo administration of beacon[47-73] (3.5 nmol/100 body weight) elicited within 60 min a marked decrease in the plasma concentration of ACTH, aldosterone and corticosterone, and a moderate lowering of the blood levels of testosterone and estradiol. This finding suggests that beacon exerts a negative modulatory action on the pituitary-adrenal axis and gonad secretory activity, whose physiological relevance remains, however, to be established

    Blood vessel-derived acellular matrix for vascular graft application

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    To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm) blood vessels, this study aimed to develop acellular matrix- (AM-) based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs) were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old) received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm). The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels
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