No abstract

Abstract. Embryo-derived tissues, such as umbilical cord (UC), can represent attractive sources of mesenchymal stem cells because their use is not related to any ethical issue. Abundant experimental evidence has already shown that Wharton's jelly contains cells able to differentiate in vitro into adipocytes, chondrocytes, osteocytes and neurons. Human UCs were obtained from term caesarean deliveries and processed within 24 h. Cells derived from the Wharton's jelly expressing mesenchymal markers, such as CD105, but not KDR and CD31 antigens, have been selected by positive and negative immunoseparation. These cells were characterized by an elongated shape and a good proliferation rate. Moreover, they were, at least in part, of fetal origin, as demonstrated by the expression of Sry mRNA. The expression of Myf5 and MyoD was detected after 7 and 11 days of in vitro myogenic induction, respectively. At two weeks from cell injection in the tibialis anterior muscle, previously damaged with bupivacaine, skeletal muscle appeared completely repaired and transplanted cells were present in the muscle for two weeks and differentiated into skeletal muscle cells, as demonstrated by the co-localization of HLA 1 and sarcomeric tropomyosine antigens. These observations provide the first demonstration that CD105(+)/CD31(-)/KDR(-) cells are able not only to differentiate in vivo towards the myogenic lineage, but also to contribute to the muscle regenerative process.

Several attemps have been performed to achieve a suitable tracheal replacement for the treatment of different conditions characterized by a lack of sufficient tissue for surgical reconstruction. Actually, tracheal homografts can induce long-term stenosis and their growth potential is not known. Thus, in this work porcine tracheal matrices have been obtained by a detergent-enzymatic method. The treatment decreased the antigenicity of matrices which were able to support the in vitro adhesion of both chondrocytes and tracheal epithelial cells. On the contrary, only few cells were observed in tracheal matrices prepared with formalin, Thimerosal, and acetone, suggesting that the long-term stenosis occuering in vivo is probably because of an insufficient cell ingrowth. In summary, our results indicate that the detergent-enzymatic method allows us to obtain tracheal matrices which can function as a promising support to achieve an in vitro tissue-engineered cell-matrix construc

Bioengineered tracheal matrices displayed similar structural and mechanical characteristics to native tracheas and excite no immune response to 30 days when implanted as allografts or xenografts. This method holds great promise for the future of tissue-engineered airway replacement.

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor ( VEGF) and fibroblast growth factor-2 (FGF- 2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro pro-angiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG- II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide- Y, vasoactive intestinal peptide ( VIP), pituitary adenylate cyclase- activating polypeptide ( PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF ( ANG- II, ETs, PAMP, resistin, VIP and PACAP) and/ or FGF-2 systems ( PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF- 2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis