We have recently isolated stem cells deriving from the olfactory bulbs of adult patients undergoing particularly invasive neurosurgery. After improving our experimental conditions, we have now obtained neural stem cells according to clonal analysis. The cells can be expanded, established in continuous cell lines and differentiated into the three classical neuronal phenotypes (neurons, astrocytes, and oligodendrocytes). Also, after exposition to leukemia inhibitory factor, we are able to improve the number of neurons, an ideal biological source for transplantation in various neurodegenerative disorders. Stem

SUMMARY:Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angioblasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11-to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [vWF], and fms-like tyrosine kinase-1 [Flk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]). The cell linings of these structures showed ultrastructural evidence of endothelial differentiation. The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34ϩ/CD31Ϫ), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing CD31 and vWF. Furthermore, the CD34ϩ/CD31ϩ cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34ϩ/CD31Ϫ endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering. (Lab Invest 2001, 81:875-885).

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The proliferation of human embryonic and adult stem cells is controlled by extrinsic factors such as epidermal growth factor (EGF) and fibroblast growth factor (bFGF). Their differentiation, instead, is clearly determined by a family of neuropoietic factors including ciliary neurotrophic factor (CNTF), leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6). The results of this study show the capability of the interleukin-6 to delay the differentiation processes and to improve significantly the proliferation condition of embryonic neural stem cells. Besides, clonal analysis shows that the selfrenewing capacity and the multipotentiality of human neural stem cells are not modified by the presence of IL-6 during early and later culture passages. This is an important demonstration of the high clonogenic potential of IL-6 in human embryonic neural stem cells (heCNS-SC), whose capacity to secrete IL-6 we have Jinally, demonstrated.