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Wharton's jelly (WJ) is a rich source of multiple-lineage differentiating cells, recently proposed for cell replacement therapy. However, their ability to integrate into the cardiac tissue has not been elucidated, yet. We employed in vitro cardiac transplantation models to investigate the capacity of a novel population of human WJ-derived mesenchymal stem cells (nMSCs) to integrate into both living and ischemic cardiac tissue. NMSCs were characterized for the expression of stem/progenitor cell genes and proteins, as well as for multi-lineage differentiation potential. To assess their integration properties, nMSCs were cocultured with either living or ischemic embryonic murine ventricular slices. Immunohistochemical analyses were performed on cryosections of cocultured preparations to allow human cells tracking within the cocultures. Results showed that nMSCs shared MSC and endothelial colony-forming cell characteristics at gene, protein, and functional levels. NMSCs were markedly chemoattracted towards the ventricular slices, integrating robustly into the depth of both living and ischemic cardiac tissue. In conclusion, the functional ability of WJ-derived cells to populate the cardiac tissue could be validated in vitro. The transplantation models described could be further used to depict the mechanisms of WJ-derived cells integration into the cardiac tissue, contributing to optimization of reliable cell therapies for cardiac repair.

Cardiac function is increasingly studied using murine models. However, current multicellular preparations to investigate contractile properties have substantial technical and biological limitations and are especially difficult to apply to the developing murine heart.Newborn murine hearts were cut with a vibratome into viable tissue slices. The structural and functional integrity of the tissue was shown by histology, ATP content and sharp electrode recordings.Within the first 48 hours after slicing structure remained intact without induction of apoptosis. ATP concentrations and action potential parameters were comparable to those of physiological tissue. Isometric force measurements demonstrated a physiological force-frequency relationship with a ;primary-phase' negative force-frequency relationship up to 1-2 Hz and a ;secondary-phase' positive force-frequency relationship up to 8 Hz. (-)-Isoproterenol (10(-6) mol/l) increased active force to 251 +/- 35% (n=15) of baseline values and shortened relaxation times indicating a preserved beta-adrenergic regulation of contraction. Changes of the force-frequency relationship after application of ryanodine and nifedipine indicated functionality of calcium release from the sarcoplasmic reticulum and of L-type calcium channels.Generation of viable, physiological intact ventricular slices from neonatal hearts is feasible and provides a robust model to study loaded contractions.