enter replicative senescence almost undetectably upon starting in vitro culturing. amniotic also called perinatal stem cells, these multipotent stem cells are found in amniotic fluid and umbilical cord blood. these stem cells are very active, expand extensively without feeders and are not tumorigenic. amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines. amniotic stem cells are a topic of active research. use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. roman catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the vatican newspaper "osservatore romano" called amniotic stem cells "the future of medicine". it is possible to collect amniotic stem cells for donors or for autologous use: the first us amniotic stem cells bank was opened in 2009 in medford, ma, by biocell center corporation and collaborates with various hospitals and universities all over the world. induced pluripotent main article: induced pluripotent stem cell adult stem cells have limitations with their potency; unlike embryonic stem cells (escs), they are not able to differentiate into cells from all three germ layers. as such, they are deemed multipotent. however, reprogramming allows for the creation of pluripotent cells, induced pluripotent stem cells (ipscs), from adult cells. these are not adult stem cells, but somatic cells (e.g. epithelial cells) reprogrammed to give rise to cells with pluripotent capabilities. using genetic reprogramming with protein transcription factors, pluripotent stem cells with esc-like capabilities have been derived. the first demonstration of induced pluripotent stem cells was conducted by shinya yamanaka and his colleagues at kyoto university. they used the transcription factors oct3/4, sox2, c-myc, and klf4 to reprogram mouse fibroblast cells into pluripotent cells. subsequent work used these factors to induce pluripotency in human fibroblast cells. junying yu, james thomson, and their colleagues at the university of wisconsin–madison used a different set of factors, oct4, sox2, nanog and lin28, and carried out their experiments using cells from human foreskin. however, they were able to replicate yamanaka's finding that inducing pluripotency in human cells was possible. induced pluripotent stem cells differ from embryonic stem cells. they share many similar properties, such as pluripotency and differentiation potential, the expression of pluripotency genes, epigenetic patterns, embryoid body and teratoma formation, and viable chimera formation, but there are many differences within these properties. the chromatin of ipscs appears to be more "closed" or methylated than that of escs. similarly, the gene expression pattern between escs and ipscs, or even ipscs sourced from different origins. there are thus questions about the "completeness" of reprogramming and the somatic memory of induced pluripotent stem cells. despite this, inducing somatic cells to be pluripotent appears to be viable. as a result of the success of these experiments, ian wilmut, who helped create the first cloned animal dolly the sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research. ipscs has helped the field of medicine significantly by finding numerous ways to cure diseases. since human ipscc has given the advantage to make in vitro models to study toxins and pathogenesis. furthermore, induced pluripotent stem cells provide several therapeutic advantages. like escs, they are pluripotent. they thus have great differentiation potential; theoretically, they could produce any cell within the human body (if reprogramming to pluripotency was "complete"). moreover, unlike escs, they potentially could allow doctors to create a pluripotent stem cell line for each individual patient. frozen blood samples can be used as a valuable source of induced pluripotent stem cells. patient specific stem cells allow for the screening for side effects before drug treatment, as well as the reduced risk of transplantation rejection. despite their current limited use therapeutically, ipscs hold great potential for future use in medical treatment and research. cell cycle control the key factors controlling the cell cycle also regulate pluripotency. thus, manipulation of relevant genes can maintain pluripotency and reprogram somatic cells to an induced pluripotent state. however, reprogramming of somatic cells is often low in efficiency and considered stochastic. with the idea that a more rapid cell cycle is a key component of pluripotency, reprogramming efficiency can be improved. methods for improving pluripotency through manipulation of cell cycle regulators include: overexpression of cyclin d/cdk4, phosphorylation of sox2 at s39 and s253, overexpression of cyclin a and cyclin e, knockdown of rb, and knockdown of members of the cip/kip family or the ink family. furthermore, reprogramming efficiency is correlated with the number of cell divisions happened during the stochastic phase, which is suggested by the growing inefficiency of reprogramming of older or slow diving cells. lineage lineage is an important procedure to analyze developing embryos. since cell lineages shows the relationship between cells at each division. this helps in analyzing stem cell lineages along the way which helps recognize stem cell effectiveness, lifespan, and other factors. with the technique of cell lineage mutant genes can be analyzed in stem cell clones that can help in genetic pathways. these pathways can regulate how the stem cell perform. to ensure self-renewal, stem cells undergo two types of cell division (see stem cell division and differentiation diagram). symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. it is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells. an alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. stem cells differentiate when they leave that niche or no longer receive those signals. studies in drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating. therapies main article: stem cell therapy stem cell therapy is the use of stem cells to treat or prevent a disease or condition. bone marrow transplant is a form of stem cell therapy that has been used for many years because it has proven to be effective in clinical trials. stem cell implantation may help in strengthening the left-ventricle of the heart, as well as retaining the heart tissue to patients who have suffered from heart attacks in the past. advantages stem cell treatments may lower symptoms of the disease or condition that is being treated. the lowering of symptoms may allow patients to reduce the drug intake of the disease or condition. stem cell treatment may also provide knowledge for society to further stem cell understanding and future treatments. the physicians' creed would be to do no injury, and stem cells make that simpler than ever before. surgical processes by their character are harmful. tissue has to be dropped as a way to reach a successful outcome. one may prevent the dangers of surgical interventions using stem cells. additionally, there's a possibility of disease, and whether the procedure fails, further surgery may be required. risks associated with anesthesia can also be eliminated with stem cells. on top of that, stem cells have been harvested from the patient's body and redeployed in which they're wanted. since they come from the patient's own body, this is referred to as an autologous treatment. autologous remedies are thought to be the safest because there's likely zero probability of donor substance rejection. disadvantages stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. one approach to avoid the second possibility is to use stem cells from the same patient who is being treated. pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. it is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. undifferentiated cells can create tissues other than desired types. some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. fetal proper stem cells form tumors despite multipotency. ethical concerns are also raised about the practice of using or researching embryonic stem cells. harvesting cells from the blastocyst result in the death of the blastocyst. the concern is whether or not the blastocyst should be considered as a human life. the debate on this issue is mainly a philosophical one, not a scientific one. stem cell tourism stem cell tourism is the part of the medical tourism industry in which patients travel to obtain stem cell procedures. the united states has had an explosion of "stem cell clinics". stem cell procedures are highly profitable for clinics. the advertising sounds authoritative but the efficacy and safety of the procedures is unproven. patients sometimes experience complications, such as spinal tumors and death. the high expense can also lead to financial problems. according to researchers, there is a need to educate the public, patients, and doctors about this issue. according to the international society for stem cell research, the largest academic organization that advocates for stem cell research, stem cell therapies are under development and cannot yet be said to be proven. doctors should inform patients that clinical trials continue to investigate whether these therapies are safe and effective but that unethical clinics present them as proven. research some of the fundamental patents covering human embryonic stem cells are owned by the wisconsin alumni research foundation (warf) – they are patents 5,843,780, 6,200,806, and 7,029,913 invented by james a. thomson. warf does not enforce these patents against academic scientists, but does enforce them against companies. in 2006, a request for the us patent and trademark office (uspto) to re-examine the three patents was filed by the public patent foundation on behalf of its client, the non-profit patent-watchdog group consumer watchdog (formerly the foundation for taxpayer and consumer rights). in the re-examination process, which involves several rounds of discussion between the uspto and the parties, the uspto initially agreed with consumer watchdog and rejected all the claims in all three patents, however in response, warf amended the claims of all three patents to make them more narrow, and in 2008 the uspto found the amended claims in all three patents to be patentable. the decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not. consumer watchdog appealed the granting of the '913 patent to the uspto's board of patent appeals and interferences (bpai) which granted the appeal, and in 2010 the bpai decided that the amended claims of the '913 patent were not patentable. however, warf was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in january 2013 the amended claims were allowed. in july 2013, consumer watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the us court of appeals for the federal circuit (cafc), the federal appeals court that hears patent cases. at a hearing in december 2013, the cafc raised the question of whether consumer watchdog had legal standing to appeal; the case could not proceed until that issue was resolved. investigations diseases and conditions where stem cell treatment is being investigated. diseases and conditions where stem cell treatment is being investigated include: diabetes androgenic alopecia and hair loss rheumatoid arthritis parkinson's disease alzheimer's disease respiratory disease osteoarthritis stroke and traumatic brain injury repair learning disability due to congenital disorder spinal cord injury repair heart infarction anti-cancer treatments baldness reversal replace missing teeth repair hearing restore vision and repair damage to the cornea amyotrophic lateral sclerosis crohn's disease wound healing male infertility due to absence of spermatogonial stem cells. in recent studies, scientist have found a way to solve this problem by reprogramming a cell and turning it into a spermatozoon. other studies have proven the restoration of spermatogenesis by introducing human ipsc cells in mice testicles. this could mean the end of azoospermia. female infertility: oocytes made from embryonic stem cells. scientists have