cells to quickly grow in number, but not size, which is important for early embryo development. In ESCs, cyclin A and cyclin E proteins involved in the G1/S transition are always expressed at high levels. Cyclin-dependent kinases such as CDK2 that promote cell cycle progression are overactive, in part due to downregulation of their inhibitors. Retinoblastoma proteins that inhibit the transcription factor E2F until the cell is ready to enter S phase are hyperphosphorylated and inactivated in ESCs, leading to continual expression of proliferation genes. These changes result in accelerated cycles of cell division. Although high expression levels of pro-proliferative proteins and a shortened G1 phase have been linked to maintenance of pluripotency, ESCs grown in serum-free 2i conditions do express hypo-phosphorylated active Retinoblastoma proteins and have an elongated G1 phase. Despite this difference in the cell cycle when compared to ESCs grown in media containing serum these cells have similar pluripotent characteristics. Pluripotency factors Oct4 and Nanog play a role in transcriptionally regulating the embryonic stem cell cycle. Uses Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Pluripotent stem cells have shown promise in treating a number of varying conditions, including but not limited to: spinal cord injuries, age related macular degeneration, diabetes, neurodegenerative disorders (such as Parkinson's disease), AIDS, etc. In addition to their potential in regenerative medicine, embryonic stem cells provide a possible alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. There are some ethical controversies surrounding this though (see Ethical debate section below). Aside from these uses, ESCs can also be used for research on early human development, certain genetic disease, and in vitro toxicology testing. Utilizations According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering." Tissue engineering In tissue engineering, the use of stem cells are known to be of importance. In order to successfully engineer a tissue, the cells used must be able to perform specific biological functions such as secretion of cytokines, signaling molecules, interacting with neighboring cells, and producing an extracellular matrix in the correct organization. Stem cells demonstrates these specific biological functions along with being able to self-renew and