Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes

Abstract

The study of human cardiac tissue development is hampered by the lack of a suitable in vitro model. We describe the phenotypic properties of cardiomyocytes derived from human embryonic stem (ES) cells. Human ES cells were cultivated in suspension and plated to form aggregates termed embryoid bodies (EBs). Spontaneously contracting areas appeared in 8.1% of the EBs. Cells from the spontaneously contracting areas within EBs were stained positively with anti-cardiac myosin heavy chain, anti--alpha-actinin, anti-desmin, anti--cardiac troponin I (anti-cTnI), and anti-ANP antibodies. Electron microscopy revealed varying degrees of myofibrillar organization, consistent with early-stage cardiomyocytes. RT-PCR studies demonstrated the expression of several cardiac-specific genes and transcription factors. Extracellular electrograms were characterized by a sharp component lasting 30 +/- 25 milliseconds, followed by a slow component of 347 +/- 120 milliseconds. Intracellular Ca(2+) transients displayed a sharp rise lasting 130 +/- 27 milliseconds and a relaxation component lasting 200--300 milliseconds. Positive and negative chronotropic effects were induced by application of isoproterenol and carbamylcholine, respectively. In conclusion, the human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomyocytes. Establishment of this unique differentiation system may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.

Derivation and long-term culture of human parthenogenetic embryonic stem cells using human foreskin feeders

“…They are regarded as a promising resource for regenerative medicine and tissue engineering [17], given that they can differentiate into somatic cell lineages that include insulinproducing cells [18], neuronal cells [19], and myocytes [2]. However, the issue of rejection due to the induction of an immune response has limited the development and application of hES cells [20,21].…”

“…Human embryonic stem (hES) cells have tremendous potential in regenerative medicine and cell therapy because of their potential for self-renewal and multi-differentiation [1,2]. Allogeneic ES cells have been found to elicit a vigorous immune response, hence it is important to use ES cells that are matched genetically with the recipient in clinical applications.…”

Gene Therapy for Cardiac Arrhythmias

“…Recent extensive developments in the understanding of embryonic stem cells (ESCs) and induced pluripotent stem cells have accelerated cell therapy for bradycardia. Since ESCs have the potential to differentiate into cardiomyocytes, 34,35 transplantation of ESC-derived pacemaker cells induced spontaneous ectopic beats. 36,37 …”

Directed differentiation of human embryonic stem cells towards a pancreatic cell fate

“…To date, while many studies have reported that hESCs could be efficiently induced to differentiate into mesodermal and ectodermal lineages, such as cardiomyocytes [1], endothelial cells [2], blood cells [3] and nerve cells [4], few reports have focused on the conversion of hESCs into endodermal lineages, particularly into pancreatic cell types [5][6][7][8], which may provide a limitless stock of insulin-producing cells to treat type 1 diabetes. Moreover, despite increasing knowledge on pancreatic development, there is still debate regarding the origin of beta cells and the markers that can be used to identify their progenitors [9].…”