Starlab NV/SA was a multidisciplinary, blue sky research institute established to serve as an incubator for long-term and basic research in the spirit of Bell Labs , MIT Media Lab , Xerox PARC , and Interval Research . Its primary headquarters was based in Brussels, Belgium from 1996 to 2001. A second base of operations, Starlab Barcelona, was established in 2000 and remains in operation.
86-514: At its peak, Starlab employed over 130 scientists from thirty-six nationalities. Starlab projects included intelligent clothing, stem cell research, emotics, transarchitecture, robotics , theoretical physics , e.g., the possibility of time travel , consciousness , quantum computation , quantum information , art, artificial intelligence , neuroscience , new media , biophysics , materials science , protein folding , nanoelectronics , and wearable computing. These research lines were grouped under
172-478: 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. 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
258-402: A blastocyst that a few trophectoderm cells can be removed without disturbing the developing blastocyst. These cells can be tested for chromosome aneuploidy using preimplantation genetic screening (PGS), or specific conditions such as cystic fibrosis , often known as preimplantation genetic diagnosis (PGD). In an embryo transfer procedure following an initial ultrasound , a speculum
344-536: A different business strategy, focusing on specialized, direct contracts with ESA under support of the Catalan and Spanish Governments. Founded by Manel Adell , [Giulio Ruffini, and Ana Maiques ,Barcelona maintains the interdisciplinary spirit of Starlab Brussels, but focuses on neuroscience technologies and applications. The lab has been awarded the Barcelona Innovation prize and other awards. Some of
430-423: A distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo . There is considerable debate as to whether some proposed adult cell populations are truly stem cells. Embryonic stem cells (ESCs) are the cells of the inner cell mass of a blastocyst , formed prior to implantation in
516-499: A fertilized egg for five days before transferring it into the uterus. It can be a more viable method of fertility treatment than traditional IVF. The inner cell mass of blastocysts is the source of embryonic stem cells , which are broadly applicable in stem cell therapies including cell repair, replacement and regeneration. Assisted zona hatching may also be used in IVF and other fertility treatments. The name "blastocyst" arises from
602-752: 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
688-471: A method to convert mature body cells back into stem cells. These were termed induced pluripotent stem cells (iPSCs). The term stem cell was coined by Theodor Boveri and Valentin Haecker in late 19th century. Pioneering works in theory of blood stem cell were conducted in the beginning of 20th century by Artur Pappenheim , Alexander Maximow , Franz Ernst Christian Neumann . The key properties of
774-864: 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
860-451: A reservoir group of progenitor cells . These cells transition to a neurogenic state and start to divide asymmetrically to produce a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from radial glial cells is called neurogenesis . The radial glial cell, has a distinctive bipolar morphology with highly elongated processes spanning
946-588: 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
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#17327758883861032-482: 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 p21 , p27 , and p57 . Furthermore, regulators of Cdk4 and Cdk6 activity, such as members of
1118-423: A specific cell type. They do not contribute to the extraembryonic membranes or to the placenta . During embryonic development the cells of the inner cell mass continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as ' neurectoderm ', which will become the future central nervous system (CNS). Later in development, neurulation causes
1204-440: A stem cell population is maintained (does not shrink in size): 1. Asymmetric cell division : a stem cell divides into one mother cell, which is identical to the original stem cell, and another daughter cell, which is differentiated. When a stem cell self-renews, it divides and disrupts the undifferentiated state. This self-renewal demands control of cell cycle as well as upkeep of multipotency or pluripotency, which all depends on
1290-541: A stem cell were first defined by Ernest McCulloch and James Till at the University of Toronto and the Ontario Cancer Institute in the early 1960s. They discovered the blood-forming stem cell, the hematopoietic stem cell (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in
1376-568: 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
1462-483: 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:
1548-444: A woman is pregnant. More hCG is secreted in a multiple pregnancy. Blood tests of hCG can also be used to check for abnormal pregnancies. In vitro fertilization (IVF) is an alternative to traditional in vivo fertilization for fertilizing an egg with sperm and implanting that embryo into a female's womb. For many years the embryo was inserted into the uterus two to three days after fertilization. However at this stage of development it
1634-459: 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
1720-587: Is a spinoff from Starlab Barcelona (2011) developing brain stimulation solutions for the clinical sector. It is currently creating personalized computational brain stimulation technologies within the Neurotwin (AD) and Galvani (focal epilepsy) projects. Starlab was featured in a Discovery Channel Special Stem cell In multicellular organisms , stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of
1806-542: 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
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#17327758883861892-422: Is also defined by the expression of several 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
1978-419: Is carried out in part by fibroblast growth factor (FGF) signaling which generates a MAP kinase pathway to alter cellular genomes. Further segregation of blastomeres into the trophectoderm and inner cell mass are regulated by the homeodomain protein, Cdx2 . This transcription factor represses the expression of Oct4 and Nanog transcription factors in the trophoblast . These genomic alterations allow for
2064-410: 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
2150-428: Is made possible through structural changes in both the blastocyst and endometrial wall. The zona pellucida surrounding the blastocyst breaches, referred to as hatching . This removes the constraint on the physical size of the embryonic mass and exposes the outer cells of the blastocyst to the interior of the uterus. Furthermore, hormonal changes in the mother, specifically a peak in luteinizing hormone (LH), prepare
2236-412: 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
2322-455: 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
2408-424: Is restricted. Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require
2494-615: Is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew. Properties of stem cells can be illustrated in vitro , using methods such as clonogenic assays , in which single cells are assessed for their ability to differentiate and self-renew. Stem cells can also be isolated by their possession of
2580-408: 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
2666-408: Is very difficult to predict which embryos will develop best, and several embryos were typically implanted. Several implanted embryos increased the likelihood of a developing fetus but also led to the development of multiple fetuses. This was a major problem and drawback for using embryos in IVF. The use of blastocysts for human IVF has proved successful. A blastocyst is implanted five to six days after
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2752-462: The Greek βλαστός blastós ("a sprout") and κύστις kýstis ("bladder, capsule"). The blastocyst stage occurs between 5 and 9 days after conception. During embryonic development , after fertilization (approximately 5–6 days in the human), the cells of the morula begin to undergo cell differentiation , and the morula changes into the blastocyst by pumping fluid to grow a lumen . In
2838-528: The University of Toronto and the Ontario Cancer Institute in the 1960s. As of 2016 , the only established medical therapy using stem cells is hematopoietic stem cell transplantation , first performed in 1958 by French oncologist Georges Mathé . Since 1998 however, it has been possible to culture and differentiate human embryonic stem cells (in stem-cell lines ). The process of isolating these cells has been controversial , because it typically results in
2924-408: The inner cell mass and a fluid-filled cavity or lumen known as the blastocoel . In the late blastocyst, the trophectoderm is known as the trophoblast . The trophoblast gives rise to the chorion and amnion , the two fetal membranes that surround the embryo. The placenta derives from the embryonic chorion (the portion of the chorion that develops villi ) and the underlying uterine tissue of
3010-466: The inner cell mass during the blastocyst stage of embryonic development , around days 5–14. These have stem-cell capability. In vivo , they eventually differentiate into all of the body's cell types (making them pluripotent ). This process starts with the differentiation into the three germ layers – the ectoderm , mesoderm and endoderm – at the gastrulation stage. However, when they are isolated and cultured in vitro , they can be kept in
3096-629: The intellectual property generated by Starlab research projects was purchased by investors or continued at university and research centers worldwide. Philips purchased the intellectual property rights to intelligent clothing project i-wear, which won the Avantex 2000 Innovation Prize. Bioprocessors, a biotechnology spinoff, transitioned to Silicon Valley . Pajamanation , a global marketplace for outsourcing microjobs, launched in fifty countries in 2006. Starlab Barcelona (2000) currently focuses on applied research initiatives in neuroscience. Neuroelectrics
3182-434: The lumen and the inner mass of cells (the embryoblast). The inner cell mass is at the origin of embryonic stem cells . The conceptus is then known as the blastocyst. Before cell differentiation takes place there are two transcription factors , Oct-4 and nanog that are uniformly expressed in all cells, but both of these transcription factors are turned off in the trophoblast once it has formed. The outer cells of
3268-434: The morula . Compaction results from increased contractility of the actomyosin cortex , which pull cells together into a tighter configuration. Increased contractility during compaction is observed in both mouse and human embryos, but is stronger in humans, which could contribute to its fragmentation . Until this developmental stage, cells ( blastomeres ) were not specified to any particular cell lineage but, when reaching
3354-409: The trophectoderm pump sodium ions into the blastocyst, which causes water to enter through osmosis . Water accumulation between cell-cell contacts breaks them open via hydraulic fracturing . The fluid then collects into a single lumen in a process akin to Ostwald ripening to form the blastocoel , which determines the first axis of symmetry of the mammalian embryo. The side of the blastocyst where
3440-409: The 16-cell stage, cells at the surface of the embryo begin to differentiate into trophectoderm while cells with inner position initiate their differentiation into inner cell mass fate. The morula then develops by cavitation to become the blastocyst, or in many other animals the blastula. Cell differentiation then further commits the morula's cells into two types: trophectoderm cells that surround
3526-493: 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
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3612-473: The Sheep , has announced that he will abandon somatic cell nuclear transfer as an avenue of research. Blastocyst The blastocyst is a structure formed in the early embryonic development of mammals . It possesses an inner cell mass (ICM) also known as the embryoblast which subsequently forms the embryo , and an outer layer of trophoblast cells called the trophectoderm . This layer surrounds
3698-447: 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
3784-697: The acronym “BANG,” or Bits, Atoms, Neurons, Genes, later adopted by MIT Media Lab in 2002. The lab sponsored and collaborated with other labs and organized several international conferences and open research symposia. Starlab's principal investors included venture capitalist Walter de Brouwer , founder and chief executive officer, MIT Media Lab founder Nicholas Negroponte , and Pythagorus investment fund manager Johan Konings. Walter Van de Velde served as chief scientific officer. Giulio Ruffini continues to serve as scientific officer for Starlab's Barcelona division. Academic and corporate partners received shared intellectual property rights to research and patents generated by
3870-535: The blastocyst to further invade the endometrium. Implantation in the uterine wall allows for the next step in embryogenesis, gastrulation , which includes the formation of the placenta from trophoblastic cells and differentiation of the inner cell mass into the amniotic sac and epiblast . There are two types of blastomere cells: The blastocoel fluid cavity contains amino acids , growth factors , and other molecules necessary for cellular differentiation . Multiple processes control cell lineage specification in
3956-415: The blastocyst to produce the trophoblast, epiblast, and primitive endoderm. These processes include gene expression, cell signaling, cell-cell contact and positional relationships, and epigenetics . Once the inner cell mass has been established within the blastocyst, it prepares for further specification into the epiblast and primitive endoderm. This process of specification known as cell fate determination
4042-469: The blastocyst undergoes implantation , embedding into the endometrium of the uterine wall where it will undergo further developmental processes, including gastrulation . Embedding of the blastocyst into the endometrium requires that it hatches from the zona pellucida , the egg coat that prevents adherence to the fallopian tube as the pre-embryo makes its way to the uterus. The use of blastocysts in in vitro fertilization (IVF) involves culturing
4128-622: The body") stem cells, are stem cells which maintain and repair the tissue in which they are found. There are three known accessible sources of autologous adult stem cells in humans: 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
4214-597: 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. Embryonic stem cells (ESCs) have
4300-820: 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
4386-504: 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
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#17327758883864472-504: 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
4558-453: The correct nutrients to sustain them into the blastocyst phase. Embryo transfer following in vitro fertilization is a procedure in which a catheter is inserted into the vagina, guided through the cervix via ultrasound, and into the uterine cavity where the blastocysts are inserted into the womb. Blastocysts also offer an advantage because they can be used to genetically test the cells to check for genetic problems. There are enough cells in
4644-430: 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
4730-453: The destruction of the embryo. Sources for isolating ESCs have been restricted in some European countries and Canada, but others such as the UK and China have promoted the research. Somatic cell nuclear transfer is a cloning method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy. In 2006, a Japanese team led by Shinya Yamanaka discovered
4816-423: The eggs have been fertilized. After five or six days it is much easier to determine which embryos will result in healthy live births. Knowing which embryos will succeed allows just one blastocyst to be implanted, cutting down dramatically on the health risk and expense of multiple births. Now that the nutrient requirements for embryonic and blastocyst development have been determined, it is much easier to give embryos
4902-484: The endometrium to receive and envelop the blastocyst. The immune system is also modulated to allow for the invasion of the foreign embryonic cells. Once bound to the extracellular matrix of the endometrium, trophoblast cells secrete enzymes and other factors to embed the blastocyst into the uterine wall. The enzymes released degrade the endometrial lining, while autocrine growth factors such as human chorionic gonadotropin (hCG) and insulin-like growth factor (IGF) allow
4988-500: The expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells. In 2011, a female maned wolf , run over by a truck, underwent stem cell treatment at the Zoo Brasília , this being the first recorded case of the use of stem cells to heal injuries in a wild animal. The classical definition of a stem cell requires that it possesses two properties: Two mechanisms ensure that
5074-414: The extracellular matrix of the uterine wall. This interaction allows for implantation and triggers further specification into the three different cell types, preparing the blastocyst for gastrulation. The level of human chorionic gonadotropin (hCG) secreted by the blastocyst during implantation is the factor measured in a pregnancy test . hCG can be measured in both blood and urine to determine whether
5160-411: The fetal placenta, the specialized organ through which the embryo obtains maternal nourishment necessary for subsequent exponential growth. The specification of the trophoblast is controlled by the combination of morphological cues arising from cell polarity with differential activity of signaling pathways such as Hippo and Notch, and the restriction to outer cells of lineage specifiers such as CDX2. In
5246-490: 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. 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
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#17327758883865332-612: The formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. In 1991, a process that allowed the human stem cell to be isolated was patented by Ann Tsukamoto. By 1998, human embryonic stem cells were first isolated by American biologist James Thomson , which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006, Shinya Yamanaka 's team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying
5418-416: 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
5504-686: The increased risk of slow growing blood cancers (myeloid malignancies) in the elderly. Several factors appear to influence HSC aging including responses to the production of reactive oxygen species that may cause DNA damage and genetic mutations as well as altered epigenetic profiling. 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
5590-635: 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 enter replicative senescence almost undetectably upon starting in vitro culturing. Hematopoietic stem cells (HSCs) are vulnerable to DNA damage and mutations that increase with age. This vulnerability may explain
5676-423: The inner cell mass forms is called the embryonic pole, and the opposite side is the abembryonic pole. The blastocoel , trophectoderm , and inner cell mass are hallmarks of the blastocyst. Implantation is critical to the survival and development of the early human embryo. It establishes a connection between the mother and the early embryo which will continue through the remainder of the pregnancy. Implantation
5762-619: 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
5848-565: The lab. Starlab's business model depended largely upon third-party investment to sustain its operations. When the dot-com bubble burst, the loss of a critical group of investors forced the lab to close its doors in 2001. The lab's assets were liquidated, and the former embassy building inhabited by the lab was purchased by the Brussels regional government. The surviving research division in Barcelona, Starlab DF2, or "Deep Future 2," adopted
5934-499: The mother. The corresponding structure in non-mammalian animals is an undifferentiated ball of cells called the blastula . In humans, blastocyst formation begins about five days after fertilization when a fluid-filled cavity opens up in the morula , the early embryonic stage of a ball of 16 cells . The blastocyst has a diameter of about 0.1–0.2 mm and comprises 100-200 cells following 7-8 rounds of cleavage (cell division without cell growth). About seven days after fertilization,
6020-503: The mouse, primordial germ cells are specified from epiblast cells, a process that is accompanied by extensive genome -wide epigenetic reprogramming. Reprogramming involves global DNA demethylation and chromatin reorganization resulting in cellular totipotency . The process of genome -wide demethylation involves the DNA base excision repair pathway. Trophoblasts express integrin on their cell surfaces which allow for adhesion to
6106-439: 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
6192-494: The neurectoderm to form the neural tube . At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell . The neural stem cells self-renew and at some point transition into radial glial progenitor cells (RGPs). Early-formed RGPs self-renew by symmetrical division to form
6278-566: The presence of leukemia inhibitory factor (LIF) in serum media. A drug cocktail containing inhibitors to GSK3B and the MAPK/ERK pathway , called 2i, has also been shown to maintain pluripotency in stem cell culture. Human ESCs are grown on a feeder layer of mouse embryonic fibroblasts and require the presence of basic fibroblast growth factor (bFGF or FGF-2). Without optimal culture conditions or genetic manipulation, embryonic stem cells will rapidly differentiate. A human embryonic stem cell
6364-415: The progressive specification of both epiblast and primitive endoderm lineages at the end of the blastocyst phase of development preceding gastrulation. Much of the research conducted on these early embryonic stages is on mouse embryos and specific factors may differ between mammals. During implantation, the trophoblast gives rise to extraembryonic membranes and cell types that will eventually form most of
6450-435: 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. 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: Adult stem cells, also called somatic (from Greek σωματικóς, "of
6536-422: The same stem cell. They are the earliest type of cell in a cell lineage . They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells , which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type. In mammals , roughly 50 to 150 cells make up
6622-403: The skin epithelium , and mesenchymal stem cells , which maintain bone, cartilage , muscle and fat cells. Adult stem cells are a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into. Research into stem cells grew out of findings by Canadian biologists Ernest McCulloch , James Till and Andrew J. Becker at
6708-527: The spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student Andrew John Becker and senior scientist Louis Siminovitch , confirmed that each lump did in fact arise from a single cell. Their results were published in Nature in 1963. In that same year, Siminovitch
6794-520: The stem cell. H. Stem cells use telomerase , a protein that restores telomeres , to protect their DNA and extend their cell division limit (the Hayflick limit ). Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell. In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs)
6880-501: The stem-cell stage and are known as embryonic stem cells (ESCs). Adult stem cells are found in a few select locations in the body, known as niches , such as those in the bone marrow or gonads . They exist to replenish rapidly lost cell types and are multipotent or unipotent, meaning they only differentiate into a few cell types or one type of cell. In mammals, they include, among others, hematopoietic stem cells , which replenish blood and immune cells, basal cells , which maintain
6966-478: The thickness of the neural tube wall. It shares some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP). The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone , adjacent to the developing ventricular system . Neural stem cells are committed to the neuronal lineages ( neurons , astrocytes , and oligodendrocytes ), and thus their potency
7052-457: The uterus the zona pellucida surrounding the blastocyst breaks down, allowing it to implant into the uterine wall. Implantation marks the end of the germinal stage of embryogenesis, and the beginning of gestation . The zygote undergoes several rounds of mitosis . After the 3rd cleavage division, the embryo begins the process of compaction, which, in human, is only completed when the embryo consists of 8-16 cells, then becoming known as
7138-443: The uterus. In human embryonic development the blastocyst stage is reached 4–5 days after fertilization , at which time it consists of 50–150 cells. ESCs are pluripotent and give rise during development to all derivatives of the three germ layers : ectoderm , endoderm and mesoderm . In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for
7224-805: Was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized. The first therapy using stem cells was a bone marrow transplant performed by French oncologist Georges Mathé in 1956 on five workers at the Vinča Nuclear Institute in Yugoslavia who had been affected by a criticality accident . The workers all survived. In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists Martin Evans and Matthew Kaufman . This allowed
7310-625: 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
7396-462: 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,
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