RESUMO
We previously demonstrated that after a severe cryoinjury to the right ventricle of the heart, adult MRL mice display structural and functional recovery with myocardial tissue replacement resembling that seen in amphibians. The control non-regenerating adult C57BL/6 (B6) mouse shows a predominant scar response. In the present study, radiation chimeras reconstituted with fetal liver cells from either healer MRL or nonhealer B6 mice were generated to test for a transfer of phenotype. Allogeneic MRL fetal liver cells were injected into x-irradiated (9 Gy) B6 mice and B6 fetal liver cells were injected into x-irradiated MRL mice. In these allogeneic chimeras, the healing response to cardiac cryoinjury was predominantly of the donor phenotype. Thus, MRL fetal liver cells transferred the healing phenotype to the B6 nonhealer with the appearance of Y-chromosome positive, donor-derived cardiomyocytes in the injury site and MRL-like healing with little scar. Similarly, B6 fetal liver cells transferred the nonhealing phenotype to the MRL with little cardiomyocyte growth and an acellular B6-like scar. These results are in contrast to the ear hole closure response which was of the recipient phenotype. We conclude that, in the case of the heart, fetal liver-derived stem cells regulate regenerative healing.
Assuntos
Hepatócitos/transplante , Miócitos Cardíacos/fisiologia , Regeneração/fisiologia , Quimeras de Transplante/fisiologia , Função Ventricular , Animais , Cicatriz/fisiopatologia , Feminino , Feto/citologia , Ventrículos do Coração/lesões , Hepatócitos/fisiologia , Camundongos , Regeneração/efeitos da radiação , Irradiação Corporal TotalRESUMO
Over the past several years many mechanisms by which myocardial replacement could be achieved have been described. These include resident cardiac stem cells or circulating stem cells that can either differentiate into, or fuse to cardiomyocytes, or mature cells that can transdifferentiate into cardiomyocytes. However, the fact remains that after injury to the heart, the overriding response is scar formation with little myocardial replacement. One exception to this response is the MRL mouse, which heals with little scarring and shows nearly full myocardial replacement after injury. Results obtained with this model will be discussed.
