Embryonic stem cells and cardiomyocyte differentiation: phenotypic and molecular analyses

Abstract

Heart disease and failure are often characterized by a loss of functioning cardiomyocytes, which are terminally differentiated and show a very limited capacity for regeneration. Cardiac transplantation is currently the treatment of choice for end-stage heart failure; however, the number of available donor organs limits this treatment option to a minority of patients [1]. The development of new therapeutic paradigms for heart failure and alternative thera- AbstractEmbryonic stem (ES) cell lines, derived from the inner cell mass (ICM) of blastocyst-stage embryos, are pluripotent and have a virtually unlimited capacity for self-renewal and differentiation into all cell types of an embryoproper. Both human and mouse ES cell lines are the subject of intensive investigation for potential applications in developmental biology and medicine. ES cells from both sources differentiate in vitro into cells of ecto-, endoand meso-dermal lineages, and robust cardiomyogenic differentiation is readily observed in spontaneously differentiating ES cells when cultured under appropriate conditions. Molecular, cellular and physiologic analyses demonstrate that ES cell-derived cardiomyocytes are functionally viable and that these cell derivatives exhibit characteristics typical of heart cells in early stages of cardiac development. Because terminal heart failure is characterized by a significant loss of cardiomyocytes, the use of human ES cell-derived progeny represents one possible source for cell transplantation therapies. With these issues in mind, this review will focus on the differentiation of pluripotent embryonic stem cells into cardiomyocytes as a developmental model, and the possible use of ES cell-derived cardiomyocytes as source of donor cells.

Neuregulin-1 promotes cardiomyocyte differentiation of genetically engineered embryonic stem cell clones

“…Spontaneous in vitro differentiation of ESCs into CMs normally requires an initial two-day aggregation step to form EBs in hanging droplets, followed by suspension for five days, before cells are plated onto gelatin-coated tissue culture dishes (7)(8)(9). Within one to four days after plating, some EBs form in one or more of the beating foci, and these structures contain cells termed ESCMs.…”

Dynamic changes of gangliosides expression during the differentiation of embryonic and mesenchymal stem cells into neural cells

“…When mESCs are cultured with mouse embryonic fibroblast, feeder cells, they proliferate indefinitely and retain the potential to differentiate into various lineages of all three primary germ layers (Martin, 1981). Various studies conducted to differentiate mESCs into neuronal cells, cardiomyocytes, muscle cells, and insulin secreting cells (He et al, 2005;Milne et al, 2005;Wei et al, 2005). Mesenchymal stem cells (MSCs) isolated from adult bone marrow are multipotent cells and can be differentiate into cartilage, tendon, fat, or bone marrow stroma (Woodbury et al, 2000).…”

Cardiomyogenesis of embryonic stem cells upon purinergic receptor activation by ADP and ATP

“…A number of peptide growth factors, cytokines, and chemical substances have been extensively studied to target different cell receptors and signaling pathways in ES cells in order to induce cardiac restricted transcription factors and subsequently differentiation of cells into distinct populations of cardiomyocytes [18]. Purinoceptors belong to those receptors which are widely expressed in early stages of ES cell differentiation and are involved in the regulation of several basic physiological processes including stem cell proliferation, differentiation, and recruitment [23,25].…”

“…Intracellular [Ca +2 ] i exerts multiple functions in the process of cardiac cell differentiation and early heart development depending upon the amplitude, space, and time of [Ca 2+ ] i signaling. Decoding the molecular mechanism of the multifaceted roles of [Ca 2+ ] i signaling will therefore not only contribute to decipher molecular pathways of cardiogenesis but also help to elaborate protocols for highly efficient cardiomyocyte differentiation from ES cells [18][19][20][21]. During embryonic heart formation, a couple of cardiogenic factors turn on Ca 2+ -dependent signaling pathways in cardiac progenitor cells.…”