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Hypoxia is defined as a reduction in oxygen supply to a tissue below physiological levels. However, physiological hypoxic conditions occur during early embryonic development; and in adult organisms, many cells such as bone marrow stem cells are located within hypoxic niches. Thus, certain processes take place in hypoxia, and recent studies highlight the relevance of hypoxia in stem cell cancer physiology. Cellular response to hypoxia depends on hypoxia-inducible factors (HIFs), which are stabilized under low oxygen conditions. In a hypoxic context, various inducible HIF alpha subunits are able to form dimers with constant beta subunits and bind the hypoxia response elements (HRE) in the genome, acting as transcription factors, inducing a wide variety of gene expression. Typically, the HIF pathway has been shown to enhance vascular endothelial growth factor (VEGF) expression, which would be responsible for angiogenesis and, therefore, re-oxygenation of the hypoxic sites. Embryonic stem cells inhibit a severely hypoxic environment, which dictates their glycolytic metabolism, whereas differentiated cells shift toward the more efficient aerobic respiration for their metabolic demands. Accordingly, low oxygen tension levels have been reported to enhance induced pluripotent stem cell (iPS) generation. HIFs have also been shown to enhance pluripotency-related gene expression, including Oct4 (Octamer-binding transcription factor 4), Nanog and Wnt. Therefore, cell metabolism might play a role in stemness maintenance, proliferation and cell reprogramming. Moreover, in the hypoxic microenvironment of cancer cells, metabolism shifts from oxidative phosphorylation to anaerobic glycolysis, a process known as the Warburg effect, which is involved in cancer progression and malignancy.

The stromal vascular fraction (SVF) of adipose tissue is an easy to obtain source of adipose tissue-derived stem cells (ADSCs). We and others have achieved significant but suboptimal therapeutic effects with ADSCs in various settings, mainly due to low rates of differentiation into specific cell types and with the downside of undesired side effects as a consequence of the undifferentiated ADSCs. These data prompted us to find new stem cell-specific markers for ADSCs and/or subpopulations with higher differentiation potential to specific lineages. We found a subpopulation of human ADSCs, marked by c-Kit positiveness, resides in a perivascular location, and shows higher proliferative activity and self-renewal capacity, higher telomerase activity and expression, higher in vitro adipogenic efficiency, a higher capacity for the maintenance of cardiac progenitors, and higher pancreatogenic and hepatogenic efficiency independently of CD105 expression. Our data suggests that the isolation of ADSC subpopulations with anti-c-Kit antibodies allows for the selection of a more homogeneous subpopulation with increased cardioprotective properties and increased adipogenic and endodermal differentiation potential, providing a useful tool for specific therapies in regenerative medicine applications.

Ventral glands are found in the cloacal walls of male urodele amphibians except for sirenids. These glands are mucous, and secrete substances that will form part of the spermatophore used in transfer of sperm during fertilization. Ventral glands are formed by secretory and ductal portions; both possess epithelial and myoepithelial cells with different characteristics. Urodeles have cyclic reproduction, and cloacal ventral glands show seasonal differences with electron microscopy. The glycoproteins secreted by these glands have been studied by means of lectin histochemistry. The labeling was detected mainly in the nuclei, rough endoplasmic reticulum, Golgi complex, and cytosol. Secretory granules in these glands are composed by mucous glycoproteins that bind PNA lectin (which binds galactose) and SBA and HPA lectins (N‐acetylgalactosamine), UEA‐I (fucose), and LcA (glucose and/or mannose). These findings suggest that the mucins secreted by ventral glands contain both N‐ and O‐linked oligosaccharides. Ventral glands secrete higher quantity and more diverse mucous substances in the reproductive period, as confirmed by lectin‐histochemical reactions. Based on these results, the major similarity between ventral cloacal glands and accessory mammalian glands, can be established with bulbourethral glands. Microsc. Res. Tech. 45:122–129, 1999. © 1999 Wiley‐Liss, Inc.