IntroductionThe Notch signaling pathway guides cell-fate decisions in multiple developmental processes. 1,2 Intercellular communications that control the developmental fate of multipotent cells are mediated by the Notch family of transmembrane receptors in several invertebrate and vertebrate developmental systems. The Notch proteins are single-pass receptors that are activated by the Delta (or Delta-like) and Jagged/Serrate families of membrane-bound ligands. 3 To date, 4 human Notch genes have been identified and all are expressed on hematopoietic cells. 2 Also, 5 human Notch ligands, Delta-like1/3/4, and Jagged1/2 were identified, and all were shown to bind to Notch-1, Notch-2, and Notch-4. 4,5 Notch receptors are matured in the secretory pathway and presented at the cell surface as heterodimeric molecules. Interaction with ligands leads to 2 additional proteolytic cleavages that liberate the Notch intracellular domain (NICD) from the plasma membrane. NICD enters the nucleus, where it interacts with the DNA-binding protein, CSL (C-promoter binding factor [CBF]-1, Suppressor of Hairless, LAG-1; also known as recombination signal-binding protein Jk [RBP-Jk]). 6 In the absence of NICD, CSL represses transcription through interactions with a corepressor complex, containing a histone deacetylase. Upon entering the nucleus, NICD displaces the corepressor complex from CSL and replaces it with a transcriptional activation complex that includes NICD, Mastermind (MAML-1), the histone acetyltransferase p300, and, possibly, PCAF p300/CBP (cyclic AMP response element-binding protein [CREB]-binding protein)-associated factor. Notch signaling, thus, converts CSL from a repressor to an activator, leading to the transcription of target genes. The target genes include members of the Hes and HRT/ HERP/Hey families of transcriptional repressors; therefore, Notch signaling is often viewed as a transcription cascade.The classical view holds that Notch signaling controls the balance between the progenitor pool and its differentiating progeny and thus is involved in the maintenance of stem cell fate. 1,2 In fact, a number of studies have provided evidence that ligand-induced Notch signaling favored hematopoietic stem cell (HSC) selfrenewal, increased the numbers of progenitors, and promoted HSC survival. Moreover, Notch signaling may be instructive for differentiation toward a particular fate. It plays a crucial role in the hematopoietic system, especially in the regulation of the T-cell lymphoid lineage commitment 7-9 and in late stages of B-cell development. 10 Because of the key role of Notch signaling in supporting early T-cell differentiation, it was generally established that Notch concomitantly negatively regulates myeloid lineage development. The megakaryocytic and erythroid lineages are extremely linked, because they share a common bipotent progenitor called the MEP (MK/erythroid progenitor). The role of Notch in megakaryocytic and erythroid development remains a matter of debate. While some data report that Notch signaling...

Human ECFCs contribute to vascular repair. For this reason, they are considered as valuable cell therapy products in ischemic diseases. Porous scaffolds are prepared that are composed of natural polysaccharides, pullulan and dextran, by chemical crosslinking without use of organic solvents. These porous scaffolds, which have pores with an average size of 42 µm and a porosity of 21%, preserve the viability and the proliferation of cord-blood ECFCs. After 7 d of culture in porous scaffolds, ECFCs express endothelial markers (CD31 and vWf) and maintain endothelial functions. The cultured cells can be easily retrieved by enzymatic degradation of the porous scaffolds. In vitro results suggest that the porous scaffold could allow cell delivery of ECFCs for treatment of vascular diseases.