Implanted skeletal myoblasts form viable grafts in infarcted myocardium, resulting in enhanced post-MI exercise capacity and contractile function and attenuated ventricular dilation. These data illustrate that syngeneic myoblast implantation after MI improves both in vivo and ex vivo indexes of global ventricular dysfunction and deleterious remodeling and suggests that cellular implantation may be beneficial after MI.
These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans.
The higher level of alphaGal-reactive IgM suggests that xenoreactive NAbs may be the product of germ-line genes. Two-dimensional gel analysis of affinity-purified alphaGal-reactive NAb from two donors provided evidence suggesting that IgM from this subpopulation of NAb were restricted in protein charge heterogeneity.
Even if hyperacute rejection, which is mediated by human natural antibodies (nAb) and complement, could be prevented, xenoreactive human anti‐pig cellular responses may lead to delayed and/or chronic xenograft rejection. Among the cell populations participating in such rejection, NK cells have been proposed as an important component. In this study we report the in vitro cytotoxic activity of natural killer (NK) cells obtained from healthy human donors against porcine target cells. Freshly isolated peripheral blood mononuclear cells (PBMC) and purified NK cells (CD16+/CD56+, CD3‐, CD20‐, CD33‐) exhibited little or no cytotoxic activity when tested on porcine phytohemagglutinin (PHA)‐stimulated lymphoblasts or bone marrow‐ or aortic‐derived endothelial cell lines in the presence of serum‐free medium. Killing was considerably higher in the presence of human decomplemented plasma, containing xenoreactive nAb, or purified Gal(α1,3)Gal‐reactive antibodies, suggesting that antibody dependent cell‐mediated cytotoxicity (ADCC) mediated by NK cells is an important mechanism involved in xenogeneic cytotoxicity. After incubation of human PBMC for 6 days in the presence of irradiated xenogeneic porcine or allogeneic stimulator cells, or in the presence of exogenous interleukin 2 (IL‐2), the cytotoxic activity of the bulk cultures as well as that of isolated NK cells (separated from stimulated bulk cultures) against xenogeneic targets increased considerably, and corresponded to an increased NK‐specific lysis of K562 target cells. Cell surface staining and flow cytometry showed that CD16+/CD56+, CD3‐ NK cells composed ca. 25% of short‐term (6 days) xenogeneic, allogeneic, or IL‐2 stimulated bulk cultures. In summary, these data suggest that, in contrast to allogeneic cell‐ mediated killing, xenogeneic human anti‐porcine cytotoxicity includes an important contribution from NK cells.
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