transcription factors and cell surface proteins. the transcription factors oct-4, nanog, and sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency. the cell surface antigens most commonly used to identify hes cells are the glycolipids stage specific embryonic antigen 3 and 4, and the keratan sulfate antigens tra-1-60 and tra-1-81. the molecular definition of a stem cell includes many more proteins and continues to be a topic of research. by using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. they can then study these specialized adult cells in detail to try to discern complications of diseases, or to study cell reactions to proposed new drugs. because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease., however, there are currently no approved treatments using es cells. the first human trial was approved by the us food and drug administration in january 2009. however, the human trial was not initiated until october 13, 2010 in atlanta for spinal cord injury research. on november 14, 2011 the company conducting the trial (geron corporation) announced that it will discontinue further development of its stem cell programs. differentiating es cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face. embryonic stem cells, being pluripotent, require specific signals for correct differentiation – if injected directly into another body, es cells will differentiate into many different types of cells, causing a teratoma. ethical considerations regarding the use of unborn human tissue are another reason for the lack of approved treatments using embryonic stem cells. many nations currently have moratoria or limitations on either human es cell research or the production of new human es cell lines. mouse embryonic stem cells with fluorescent marker human embryonic stem cell colony on mouse embryonic fibroblast feeder layer mesenchymal stem cells human mesenchymal stem cells mesenchymal stem cells (msc) or mesenchymal stromal cells, also known as medicinal signaling cells are known to be multipotent, which can be found in adult tissues, for example, in the muscle, liver, bone marrow and adipose tissue. mesenchymal stem cells usually function as structural support in various organs as mentioned above, and control the movement of substances. msc can differentiate into numerous cell categories as an illustration of adipocytes, osteocytes, and chondrocytes, derived by the mesodermal layer. where the mesoderm layer provides an increase to the body's skeletal elements, such as relating to the cartilage or bone. the term "meso" means middle, infusion originated from the greek, signifying that mesenchymal cells are able to range and travel in early embryonic growth among the ectodermal and endodermal layers. this mechanism helps with space-filling thus, key for repairing wounds in adult organisms that have to do with mesenchymal cells in the dermis (skin), bone, or muscle. mesenchymal stem cells are known to be essential for regenerative medicine. they are broadly studied in clinical trials. since they are easily isolated and obtain high yield, high plasticity, which makes able to facilitate inflammation and encourage cell growth, cell differentiation, and restoring tissue derived from immunomodulation and immunosuppression. msc comes from the bone marrow, which requires an aggressive procedure when it comes to isolating the quantity and quality of the isolated cell, and it varies by how old the donor. when comparing the rates of msc in the bone marrow aspirates and bone marrow stroma, the aspirates tend to have lower rates of msc than the stroma. msc are known to be heterogeneous, and they express a high level of pluripotent markers when compared to other types of stem cells, such as embryonic stem cells. mscs injection leads to wound healing primarily through stimulation of angiogenesis. cell cycle control embryonic stem cells (escs) have the ability to divide indefinitely while keeping their pluripotency, which is made possible through specialized mechanisms of cell cycle control. compared to proliferating somatic cells, escs have unique cell cycle characteristics—such as rapid cell division caused by shortened g1 phase, absent g0 phase, and modifications in cell cycle checkpoints—which leaves the cells mostly in s phase at any given time. escs' rapid division is demonstrated by their short doubling time, which ranges from 8 to 10 hours, whereas somatic cells have doubling time of approximately 20 hours or longer. as cells differentiate, these properties change: g1 and g2 phases lengthen, leading to longer cell division cycles. this suggests that a specific cell cycle structure may contribute to the establishment of pluripotency. particularly because g1 phase is the phase in which cells have increased sensitivity to differentiation, shortened g1 is one of the key characteristics of escs and plays an important role in maintaining undifferentiated phenotype. although the exact molecular mechanism remains only partially understood, several studies have shown insight on how escs progress through g1—and potentially other phases—so rapidly. the cell cycle is regulated by complex network of cyclins, cyclin-dependent kinases (cdk), cyclin-dependent kinase inhibitors (cdkn), pocket proteins of the retinoblastoma (rb) family, and other accessory factors. foundational insight into the distinctive regulation of esc cell cycle was gained by studies on mouse escs (mescs). mescs showed a cell cycle with highly abbreviated g1 phase, which enabled cells to rapidly alternate between m phase and s phase. in a somatic cell cycle, oscillatory activity of cyclin-cdk complexes is observed in sequential action, which controls crucial regulators of the cell cycle to induce unidirectional transitions between phases: cyclin d and cdk4/6 are active in the g1 phase, while cyclin e and cdk2 are active during the late g1 phase and s phase; and cyclin a and cdk2 are active in the s phase and g2, while cyclin b and cdk1 are active in g2 and m phase. however, in mescs, this typically ordered and oscillatory activity of cyclin-cdk complexes is absent. rather, the cyclin e/cdk2 complex is constitutively active throughout the cycle, keeping retinoblastoma protein (prb) hyperphosphorylated and thus inactive. this allows for direct transition from m phase to the late g1 phase, leading to absence of d-type cyclins and therefore a shortened g1 phase. cdk2 activity is crucial for both cell cycle regulation and cell-fate decisions in mescs; downregulation of cdk2 activity prolongs g1 phase progression, establishes a somatic cell-like cell cycle, and induces expression of differentiation markers. in human escs (hescs), the duration of g1 is dramatically shortened. this has been attributed to high mrna levels of g1-related cyclin d2 and cdk4 genes and low levels of cell cycle regulatory proteins that inhibit cell cycle progression at g1, such as p21cipp1, p27kip1, and p57kip2. furthermore, regulators of cdk4 and cdk6 activity, such as members of the ink family of inhibitors (p15, p16, p18, and p19), are expressed at low levels or not at all. thus, similar to mescs, hescs show high cdk activity, with cdk2 exhibiting the highest kinase activity. also similar to mescs, hescs demonstrate the importance of cdk2 in g1 phase regulation by showing that g1 to s transition is delayed when cdk2 activity is inhibited and g1 is arrest when cdk2 is knocked down. however unlike mescs, hescs have a functional g1 phase. hescs show that the activities of cyclin e/cdk2 and cyclin a/cdk2 complexes are cell cycle-dependent and the rb checkpoint in g1 is functional. escs are also characterized by g1 checkpoint non-functionality, even though the g1 checkpoint is crucial for maintaining genomic stability. in response to dna damage, escs do not stop in g1 to repair dna damages but instead, depend on s and g2/m checkpoints or undergo apoptosis. the absence of g1 checkpoint in escs allows for the removal of cells with damaged dna, hence avoiding potential mutations from inaccurate dna repair. consistent with this idea, escs are hypersensitive to dna damage to minimize mutations passed onto the next generation. fetal the primitive stem cells located in the organs of fetuses are referred to as fetal stem cells. there are two types of fetal stem cells: fetal proper stem cells come from the tissue of the fetus proper and are generally obtained after an abortion. these stem cells are not immortal but have a high level of division and are multipotent. extraembryonic fetal stem cells come from extraembryonic membranes, and are generally not distinguished from adult stem cells. these stem cells are acquired after birth, they are not immortal but have a high level of cell division, and are pluripotent. adult stem cell division and differentiation a: stem cell; b: progenitor cell; c: differentiated cell; 1: symmetric stem cell division; 2: asymmetric stem cell division; 3: progenitor division; 4: terminal differentiation adult stem cells, also called somatic (from greek σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found. they can be found in children, as well as adults. there are three known accessible sources of autologous adult stem cells in humans: bone marrow, which requires extraction by harvesting, usually from pelvic bones via surgery. adipose tissue (fat cells), which requires extraction by liposuction. blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. stem cells can also be taken from umbilical cord blood just after birth. of all stem cell types, autologous harvesting involves the least risk. by definition, autologous cells are obtained from one's own body, just as one may bank their own blood for elective surgical procedures. pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues. bone marrow is a rich source of adult stem cells, which have been used in treating several conditions including liver cirrhosis, chronic limb ischemia and endstage heart failure. the quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years. much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities. dna damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. this accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see dna damage theory of aging). most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.). muse cells (multi-lineage differentiating stress enduring cells) are a recently discovered pluripotent stem cell type found in multiple adult tissues, including adipose, dermal fibroblasts, and bone marrow. while rare, muse cells are identifiable by their expression of ssea-3, a marker for undifferentiated stem cells, and general mesenchymal stem cells markers such as cd90, cd105. when subjected to single cell suspension culture, the cells will generate clusters that are similar to embryoid bodies in morphology as well as gene expression, including canonical pluripotency markers oct4, sox2, and nanog. adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants. adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses. the use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. consequently, more us government funding is being provided for adult stem cell research. with the increasing demand of human adult stem cells for both research and clinical purposes (typically 1–5 million cells per kg of body weight are required per treatment) it becomes of utmost importance to bridge the gap between the need to expand the cells in vitro and the capability of harnessing the factors underlying replicative senescence. adult stem cells are known to have a limited lifespan in vitro and to