Cardiomyocyte differentiation of mouse and human embryonic stem cells*

Abstract

Ischaemic heart disease is the leading cause of morbidity and mortality in the western world. Cardiac ischaemia caused by oxygen deprivation and subsequent oxygen reperfusion initiates irreversible cell damage, eventually leading to widespread cell death and loss of function. Strategies to regenerate damaged cardiac tissue by cardiomyocyte transplantation may prevent or limit post-infarction cardiac failure. We are searching for methods for inducing pluripotent stem cells to differentiate into transplantable cardiomyocytes. We have already shown that an endoderm-like cell line induced the differentiation of embryonal carcinoma cells into immature cardiomyocytes. Preliminary results show that human and mouse embryonic stem cells respond in a similar manner. This study presents initial characterization of these cardiomyocytes and the mouse myocardial infarction model in which we will test their ability to restore cardiac function.

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

“…(13) Recent publications have demonstrated the development of clinically suitable ex vivo differentiation protocols for obtaining insulin-producing b cells (14,15) and neuronal cells (16,17) from hESCs. Several protocols have been reported in which hESCs were directed to differentiate into musculoskeletal tissue: osteoblastic cells, (18)(19)(20)(21)(22) chondroyctic cells, (23) cardiomyocytes, (24)(25)(26)(27)(28) and skeletal myoblasts. (29) However, most of these protocols relied on using coculture with differentiated cells or complex culture conditions to induce differentiation.…”

Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth Without Conditioned Medium

“…In addition to this self-renewal ability, hESCs differentiate both in vivo and in vitro, generating representatives of all three embryonic germ layers, including neural progenitors, cardiomyocytes, trophoblast cells, endothelial cells, hematopoietic lineages, hepatocyte-like cells, osteoblasts, and insulin-expressing cells [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Because of these fundamental characteristics, hESCs hold promise for cell-based therapies for degenerative diseases.…”

Formation of Human Myocardium in the Rat Heart from Human Embryonic Stem Cells

“…First, there are welldefined protocols for the isolation and maintenance of ESCs, and they have a tremendous capacity for in vitro expansion, making them likely scalable for human applications. 23 Second, ESCs have an unquestioned ability to differentiate into functional cardiomyocytes in vitro, 17,18,21,24,25 which stands in contrast to a number of other candidate cell sources for which this capacity remains controversial. 8,26 Furthermore, human ESC (hESC)-derived cardiomyocytes possess the cellular elements required for electromechanical coupling with the host myocardium (eg, gap and adherens junctions 17,18 ), and it is therefore expected that, when transplanted, these cells could electrically integrate and contribute to systolic function.…”