Migration and differentiation of human umbilical cord stem cells after heart injury in chicken embryos.

2008, Stem Cells Dev. 2008 Mar 21 [Epub ahead of print]
Torre-Perez N, Montero JA, Zuzarte-Luis V, Garcia-Porrero JA, Rubio N, Blanco J, Nistal JF, Hurle JM.
Autors del centre relacionats: Blanco Jerónimo, Rubio Nuria.

Here we have analyzed the behavior and fate of stem cells from human umbilical cord blood (scHUCB) when grafted into the myocardial wall of normal and damaged hearts of chicken embryos. We started by characterizing the scHUCB before grafting and we found that they express precardiogenic genes including Nkx2.5, GATA4, MEF2 and SERCA2a together with un-differentiation markers as CD34 or c-kit. In grafting experiments using scHUCB labeled with DiI we observed that these cells were not rejected by the host and survived when implanted in chicken hearts, being able to migrate through the myocardial wall. By 3 days after grafting we found labeled cells with morphological characters of myocardiocytes in concordance with the identification of the expression of human genes for myosin light chain 2a (Mlc2a) and Myosin heavy chain ss (Mhcss) in the chicken heart. When a small injury was applied to the heart wall, grafted scHUCB were vigorously attracted by the damaged myocardium. This directed migration was only sustained for 12 hr after injury, time-period required for healing of the damaged heart wall. The rate of myocardial differentiation of scHUCB in damaged hearts was not significantly increased respect to that found when implanted in healthy hearts. However we found stimulation of endothelial differentiation in injured hearts deduced by the increased expression of human genes for PECAM-1 or VEGFR2 and the presence of DiI labeled endothelial cells. Together all these findings support the embryonic chicken heart as a feasible model for experimentation in stem cell therapy and emphasize the relevance of the physiological conditions of the myocardial host tissue for engraftment and differentiation of exogenously applied scHUCB.

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