Molecular Biomarkers of Embryonic Stem Cells

Abstract

Embryonic stem cells (ESCs) are pluripotent cells capable of both limitless selfrenewal and differentiation into all embryonic lineages, and thus ESCs can give rise to any adult cell type. When ESCs are stably maintained in culture and their pluripotency is strictly enforced, they can serve as an unlimited source for tissue replacement in regenerative medicine for degenerative diseases such as neural disorders, heart disease, and type I diabetes. They also offer enormous potential for drug discovery and toxicology, human developmental biology, and cancer research. Studies of human ESCs (hESCs) biology have developed rapidly since the first reports of their derivation in 1998 (Thomson et al., 1998). Many studies have tried to manipulate the growth and differentiation conditions of hESCs with variable success (Biswas and Hutchins, 2007; Hoffman and Carpenter, 2005). hESCs have been differentiated into the derivatives of all three germ layers: ectoderm, mesoderm, and endoderm. Specifically, these derivatives include cardiomyocytes, neural cells, hepatocyte-like cells, endothelial cells, pancreatic hormone expressing endocrine cells, and hematopoietic progenitor cells (Barberi et al., 2007; Carpenter et al., 2003; D'Amour et al., 2006; Levenberg et al., 2007; Lu et al., 2007; Roy et al., 2006; Wang et al., 2007), and thus hESCs have great potential for use in regenerative medicine to restore heart disease, neuronal functions, hepatic disease, blood vessels, and type I diabetes. In addition, mouse ESCs (mESCs) can generate hepatocytes (Gouon-Evans et al., 2006; Soto-Gutierrez et al., 2007), insulinproducing cells (Schroeder et al., 2006), cerebellar neurons (Salero and Hatten, 2007), and even germ cells (West et al., 2006) in vitro, suggesting that hESC can be applied much more widely to regenerative medicine in the future. On October 2010, Geron corporation in United States announced plans to initiate the phase I clinical trial of hESC-derived oligodendrocyte progenitor cells. However, the clinical application of hESCs is restricted thus far for alleged ethical and scientific reasons. First, hESC research often faces opposition from those who object to the destruction of human embryos. Second, ESC therapy potentially poses the risk of tumorigenesis. ESCs frequently form teratocarcinomas when transplanted into mice. Moreover, the ability of ESCs to provide differentiated cells for regenerative medicine will require continual maintenance of the undifferentiated stem cells for long periods in culture. However, chromosomal stability during extended cell passage cannot be guaranteed, and recent cytogenetic studies of ESCs have revealed karyotypic aberrations (Baker et al., 2007). Third, cell replacement therapies have been limited by the availability of sufficient quantities of cells for transplantation. Although there are many reports describing a method to maintain ESC properties in culture, the large-scale culture of