RESUMO
In the last few years, a major goal of cardiac research has been to drive stem cell differentiation to replace damaged myocardium. Several research groups have attempted to differentiate potential cardiac stem cells (CSCs) using bi- or three-dimensional systems supplemented with growth factors or molecules acting as differentiating substances. We hypothesize that these systems failed to induce a complete differentiation because they lacked an architectural space. In the present study, we isolated a pool of small proliferating and fibroblast-like cells from adult rat myocardium. The phenotype of these cells was assessed and the characterized cells were cultured in a collagen I/OPLA scaffold with horse serum to obtain fine myocardial differentiation. C-Kit(POS)/Sca-1(POS) CSCs fully differentiated in vitro when an environment more similar to the CSC niche was created. These experiments demonstrated an important model for the study of the biology of CSCs and the biochemical pathways that lead to myocardial differentiation. The results pave the way for a new surgical approach.
Assuntos
Células-Tronco Adultas/citologia , Diferenciação Celular/efeitos dos fármacos , Colágeno Tipo I/farmacologia , Miócitos Cardíacos/citologia , Soro , Alicerces Teciduais , Actinas/metabolismo , Células-Tronco Adultas/metabolismo , Animais , Separação Celular/métodos , Células Clonais/citologia , Células Clonais/metabolismo , Conexina 43/metabolismo , Feminino , Fator de Transcrição GATA4/metabolismo , Proteínas de Homeodomínio/metabolismo , Cavalos , Proteínas de Filamentos Intermediários/metabolismo , Proteínas com Homeodomínio LIM , Microscopia Eletrônica de Transmissão , Desenvolvimento Muscular/efeitos dos fármacos , Miocárdio/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Cadeias Pesadas de Miosina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nestina , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição , Troponina T/metabolismoRESUMO
Heart disease is the leading cause of death in the industrialized world, and stem cell therapy seems to be a promising treatment for injured cardiac tissue. To reach this goal, the scientific community needs to find a good source of stem cells that can be used to obtain new myocardium in a very period range of time. Since there are many ethical and technical problems with using embryonic stem cells as a source of cells with cardiogenic potential, many laboratories have attempted to isolate potential cardiac stem cells from several tissues. The best candidates seem to be cardiac "progenitor" and/or "stem" cells, which can be isolated from subendocardial biopsies from the same patient or from embryonic and/or fetal myocardium. Regardless of the technique used to isolate and characterize these cells, it appears that the different cells isolated from adult myocardium to date are all phenotypic variations of a unique cell type that expresses several markers, such as c-Kit, CD34, MDR-1, Sca-1, CD45, nestin, or Isl-1, in various combinations.