Migration and differentiation of human umbilical cord stem cells after heart injury in chicken embryos.
Here we have analyzed the behavior and fate of stem cells from human umbilical cord blood (scHUCBs) when grafted into the myocardial wall of normal and damaged hearts of chicken embryos. We started by characterizing the scHUCBs before grafting and we found that they express precardiogenic genes including Nkx2.5, GATA4, MEF-2, and SERCA2a together with undifferentiation markers as CD34 or c-kit. In grafting experiments using scHUCBs 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-beta (Mhc beta) in the chicken heart. When a small injury was applied to the heart wall, grafted scHUCBs were vigorously attracted by the damaged myocardium. This directed migration was only sustained for 12 h after injury, time period required for healing of the damaged heart wall. The rate of myocardial differentiation of scHUCBs in damaged hearts was not significantly increased with 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 platelet endothelial cell-adhesion molecule 1 or vascular endothelial growth factor receptor 2 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 scHUCBs.
Torre-Pérez
Nuria
N
Departamento de Anatomía y Biología Celular, Hospital Universitario Marques de Valdecilla, Universidad de Cantabria, Santander, Spain.
Montero
Juan A
JA
Zuzarte-Luis
Vanessa
V
García-Porrero
Juan A
JA
Rubio
Nuria
N
Blanco
Jerónimo
J
Nistal
Juan F
JF
Hurlé
Juan M
JM
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D015870:Gene Expression; D006335:Heart Injuries / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014470:Umbilical Cord / Q000166:cytology*