Fetal Stem Cell

Three to five days after fertilization, the microscopic hollow sphere has about 50 cells and resembles a golf ball more than a human form. Still in the fallopian tube, it is now called a blastocyst (sometimes “blastomcre”)
and is also totipolent. although this level of plasticity decreases rapidly.

   The blastocyst from a live-day-old human embryo can give rise to only a limited range of cells. his now pluripoent (a word derived from the Latin terms plures. meaning ‘many or several.” and pofrns. meaning “powerful”). Still in the fallopian tube, it will now pass through several stages and form three layers—the endoderm, the mesoderm, and the ectoderm. This stage of development is called the blastuha, when two kinds of cells—the inner cell mass (1CM) and the trophoblast—develop. Surrounding the cell is the zona pellucida, the outside cell membrane. The 1CM will form the tissues of the embryo. The trophoblast will become the placenta and choronic membrane, and will direct implantation into the mother’s uterus. By the
end of the first week, the blastocyst implants in the uterus 

    Here an amazing feat of communication takes place. The cells begin to talk to each other in an intricate manner. They touch each other or in some way signal to tell cells to differentiate into certain other types of cells. Timing is critical in establishing the basic body plan for what shall become the head and what shall become the tail. This process is called embryonic induction and occurs in three stages: primary. secondary. and tertiary. Primary induction leads to the next stage. the gastrula, in which three germ layers are
formed that become the differentiated tissues shown in Figure

• Ectoderm—the outer layer that gives rise to the outer epithelium. including hair, nails, and skin: the sense     organs; and the brain and spinal cord. Epithelium forms from the epidermis and other stru.1urcs.
• Mesoderm—the middle layer that gives rise to bones, muscle, connective tissue, the circulatory system. and most of the excretory and
reproductive systems.
• Endoderm—the inner layer that gives rise to the epithelial linings. those cells that form the linings of the body cavity. including the digestive tract, most of the respiratory tract, the urinary bladder, liver. pancreas. and some endocrine glands.

   The process of the development of the three layers is called gastrulation.
Secondary induction involves a complex communication pattern to initiate the formation of the rudimentary brain and nervous system: tertiary induction regulates the development of body organs and other structures.
The fertilized egg will continue dividing until it produces a complete organism capable of life in the uterus, or in utero. More than 200 kinds of cells will develop from a single, totipotent cell—the zygote or fertilized
egg. These cells include neurons (nerve cells); myocytes (muscle cells); epithelial (skin) cells; bl(xxl cells such as erythrocytes, monocytes, and lymphocytes; osteocytes (bone cells); and chondrocytes (cartilage
cells). Other cells essential for embryonic development include the extraembryonic tissues, placenta, and umbilical cord. 

   The blastocyst in vitro (i.e.. in the laboratory) develops in a similar and predictable way. After fertilization, the embryo develops as follows:

• Day I—Development begins 18 to 24 hours after fertilization.
• Day 2—The zygote undergoes its Iirs cleavage to produce a two- cell embryo. 24 to 25 hours after fertilization.
• Day 3—An eight-cell mass called a modular that resembles a blackberry develops 72 houm after fertilization. Now the embryo begins to control its own development, and the mother’s influences arc reduced.
• Day 4—The embryo’s cells hold close to each other in a process called compaction.

• Day 5—The cavity of the blastocyst is complete. The inner cell mass begins to separate from the outer cells, which become the trophectoderm that surrounds the blastocyst. This is the first sign of differentiation.
• Tmplantatlon—After about the fifth day. the human embryo makes a connection with the mother. This connection has been impossible to make in the laboratory, or even to monitor as it happens in the mother in vivo. However, scientists have studied implantation using the four processes of analysis of gene expression in small samples, in vitro fertilization, analysis of the clones of cultured embryos. and study of genetic markers. In humans, implantation occurs when the irophobla.st cells invade the uterine tissue, forming a syn-claustrophobia.s— something like a mcga-ccIl. The fetus secretes procolytic enzymes that dissolve the uterine epithelial cells and degrade the exracellular matrix. Implantation protects the embryo and provides its metabolic needs.

Evans student in Cambridge

Personal life

When Evans was a student in Cambridge he met his wife, Judith, at a lunch held by his aunt, wife of an astronomy professor. After they were engaged, their relationship did not go well and Judith went to live in Canada; however, a year later she returned to England and they married. In 1978, they moved from London to Cambridge with their young children, where they lived for more than 20 years before moving to Cardiff. They have one daughter and two sons. Their older son was a student at the University of Cambridge and their younger son was a boarder at Christ Church Cathedral School in Oxford and sang in Christ Church Cathedral choir.

Judith Evans, granddaughter of Christopher Williams, was appointed Member of the Order of the British Empire for her services to practice nursing in the 1993 New Year Honours She was diagnosed with breast cancer at about the time the family moved to Cardiff. She works for breast cancer charities, and Martin Evans has become a trustee of Breakthrough Breast Cancer.

• Awards and Recognition
• Life Of  Matthew H. Kaufman 

The primary result of mitosis

The primary result of mitosis is the transferring of the parent cell's genome into two daughter cells. These two cells are identical and do not differ in any way from the original parent cell. The genome is composed of a number of chromosomes—complexes of tightly coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during the S phase of interphase, the period that precedes the mitotic phase in the cell cycle where preparation for mitosis occurs.

Each chromosome now has an identical copy of itself, and together the two are called sister chromatids. The sister chromatids are held together by a specialized region of the chromosome: a DNA sequence called the centromere. The "real" process of mitosis begins when the chromosomes condense and become visible. In most eukaryotes, the nuclear membrane which segregates the DNA from the cytoplasm disintegrates into membrane vesicles. The nucleolus which make ribosomes in the cell also dissolves. The chromosomes align themselves in a line spanning the cell. Microtubules — essentially miniature strings— splay out from opposite ends of the cell and shorten, pulling apart the sister chromatids of each chromosome. As a matter of convention, each sister chromatid is now considered a chromosome, so they are renamed to daughter chromosomes. As the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends. A new nuclear membrane forms around the separated daughter chromosomes.

As mitosis completes,the cell begins cytokinesis. In animal cells, the cell pinches inward where the imaginary line used to be (the area of the cell membrane that pinches to form the two daughter cells is called the cleavage furrow), separating the two developing nuclei. In plant cells, the daughter cells will construct a new dividing cell wall between each other. Eventually, the parent cell will be split in half, giving rise to two daughter cells, each with a replica of the original genome.

Prokaryotic cells undergo a process called binary fission which is very much different from the process of mitosis, because of the non-involvement of nuclear dynamics and lack of linear chromosomes.

errors in mitosis daughter cell

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An abnormal (tripolar) mitosis (12 o'clock position) in a precancerous lesion of the stomach. H&E stain

Although errors in mitosis are rare, the process may go wrong, especially during early cellular divisions in the zygote. Mitotic errors can be especially dangerous to the organism because future offspring from this parent cell will carry the same disorder.

In nondisjunction, a chromosome may fail to separate during anaphase. One daughter cell will receive both sister chromosomes and the other will receive none. This results in the former cell having three chromosomes containing the same genes (two sisters and a homologue), a condition known as trisomy, and the latter cell having only one chromosome (the homologous chromosome), a condition known as monosomy. These cells are considered aneuploid, a condition often associated with cancer. Occasionally when cells experience nondisjunction, they fail to complete cell division and retain both nuclei in one cell, resulting in binucleated cells.[citation needed]

Mitosis is a demanding process for the cell, which goes through dramatic changes in ultrastructure, its organelles disintegrate and reform in a matter of hours, and chromosomes are jostled constantly by probing microtubules. Occasionally, chromosomes may become damaged. An arm of the chromosome may be broken and the fragment lost, causing deletion. The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation. It may reattach to the original chromosome, but in reverse orientation, causing inversion. Or, it may be treated erroneously as a c, causing chromosomal duplication. The effect of these genetic abnormalities depends on the specific nature of the error.[citation needed]

Botanische Zeitung in conjunction with Schlechtendal,

 

 In 1843 he started the weekly Botanische Zeitung in conjunction with Schlechtendal, which he edited jointly till his death. He was never a great writer of comprehensive works; no text-book exists in his name, and it would indeed appear from his withdrawal from co-operation in Hofmeister's Handbuch that he had a distaste for such efforts. In 1850, he was elected a foreign member of the Royal Swedish Academy of Sciences. In his latter years his productive activity fell off, doubtless through failing health, and he died suddenly at Tübingen on 1 April 1872.

      The standard author abbreviation Mohl is used to indicate this individual as the author when citing a botanical name.

Hugo von Mohl (8 April 1805 – 1 April 1872)

Hugo von Mohl

Hugo von Mohl (8 April 1805 – 1 April 1872) was a German botanist from Stuttgart. He was a son of the Württemberg statesman Benjamin Ferdinand von Mohl (1766–1845), the family being connected on both sides with the higher class of state officials of Württemberg. While a pupil at the gymnasium he pursued botany and mineralogy in his leisure time, till in 1823 he entered the University of Tübingen. After graduating with distinction in medicine he went to Munich, where he met a distinguished circle of botanists, and found ample material for research.

    This seems to have determined his career as a botanist, and he started in 1828 those anatomical investigations which continued till his death. In 1832 he was appointed professor of botany in Tübingen, a post which he never left. Unmarried, his pleasures were in his laboratory and library, and in perfecting optical apparatus and microscopic preparations, for which he showed extraordinary manual skill. He was largely a self-taught botanist from boyhood, and, little influenced in his opinions even by his teachers, preserved always his independence of view on scientific questions. He received many honours during his lifetime, and was elected foreign fellow of the Royal Society in 1868.

    Mohl's writings cover a period of forty-four years; the most notable of them were republished in 1845 in a volume entitled Vermischte Schriften (For lists of his works see Botanische Zeitung, 1872, p. 576, and Royal Soc. Catalogue, 1870, vol. iv.) They dealt with a variety of subjects, but chiefly with the structure of the higher forms, including both rough anatomy and minute histology. The word protoplasm was his suggestion; the nucleus had already been recognized by R. Brown and others; but Mohl showed in 1844 that the protoplasm is the source of those movements which at that time excited so much attention.

He recognized under the name of primordial utricle the protoplasmic lining of the vacuolated cell, and first described the behaviour of the protoplasm in cell division. These and other observations led to the overthrow of Schleiden's theory of origin of cells by free-cell-formation. His contributions to knowledge of the cell-wall were no less remarkable; he held the view now generally adopted of growth of cell-wall by apposition. He first explained the true nature of pits, and showed the cellular origin of vessels and of fibrous cells; he was, in fact, the true founder of the cell theory. Clearly the author of such researches was the man to collect into one volume the theory of cell-formation, and this he did in his treatise Die vegetabilische Zelle (1851), a short work translated into English (Ray Society, 1852).

    Mohl's early investigations on the structure of palms, of cycads,   and of tree ferns permanently laid the foundation of all later knowledge of this subject: so also his work on Isoetes (1840). His later anatomical work was chiefly on the stems of dicotyledons and gymnosperms; in his observations on cork and bark he first explained the formation and origin of different types of bark, and corrected errors relating to lenticels. Following on his early demonstration of the origin of stomata (1838), he wrote a classical paper on their opening and closing (1850).

Van Beneden

Édouard Joseph Louis Marie Van Beneden (Leuven, 5 March 1846 – Liège, 28 April 1910), son of Pierre-Joseph Van Beneden, was a Belgian embryologist, cytologist and marine biologist. He was professor of zoology at the University of Liège. He contributed to cytogenetics by his works on the roundworm Ascaris. In this work he discovered how chromosomes organized meiosis (the production of gametes).

Van Beneden elucidated, together with Walther Flemming and Eduard Strasburger, the essential facts of mitosis, where, in contrast to meiosis, there is a qualitative and quantitative equality of chromosome distribution to daughter cells. (See karyotype

Édouard Joseph Louis Marie Van Beneden (Leuven, 5 March 1846 – Liège, 28 April 1910)

Édouard Joseph Louis Marie Van Beneden (Leuven, 5 March 1846 – Liège, 28 April 1910), son of Pierre-Joseph Van Beneden, was a Belgian embryologist, cytologist and marine biologist. He was professor of zoology at the University of Liège. He contributed to cytogenetics by his works on the roundworm Ascaris. In this work he discovered how chromosomes organized meiosis (the production of gametes).

Van Beneden elucidated, together with Walther Flemming and Eduard Strasburger, the essential facts of mitosis, where, in contrast to meiosis, there is a qualitative and quantitative equality of chromosome distribution to daughter cells. (See karyotype).

Tree of life

     While Earth is the only place in the universe where life is known to exist, some have suggested that there is evidence on Mars of fossil or living prokaryotes. but this possibility remains the subject of considerable debate and skepticism.

     Prokaryotes have diversified greatly throughout their long existence. The metabolism of prokaryotes is far more varied than that of eukaryotes, leading to many highly distinct prokaryotic types. For example, in addition to using photosynthesis or organic compounds for energy, as eukaryotes do, prokaryotes may obtain energy from inorganic compounds such as hydrogen sulfide. This enables prokaryotes to thrive in harsh environments as cold as the snow surface of Antarctica, and as hot as undersea hydrothermal vents and land-based hot springs.

current model of the evolution of the first living organisms

Evolution of prokaryotes

The current model of the evolution of the first living organisms is that these were some form of prokaryotes, which may have evolved out of protobionts. In general, the eukaryotes are thought to have evolved later in the history of life. However, some authors have questioned this conclusion, arguing that the current set of prokaryotic species may have evolved from more complex eukaryotic ancestors through a process of simplification. Others have argued that the three domains of life arose simultaneously, from a set of varied cells that formed a single gene pool. This controversy was summarized in 2005.

T  here is no consensus among biologists concerning the position of the eukaryotes in the overall scheme of cell evolution. Current opinions on the origin and position of eukaryotes span a broad spectrum including the views that eukaryotes arose first in evolution and that prokaryotes descend from them, that eukaryotes arose contemporaneously with eubacteria and archeabacteria and hence represent a primary line of descent of equal age and rank as the prokaryotes, that eukaryotes arose through a symbiotic event entailing an endosymbiotic origin of the nucleus, that eukaryotes arose without endosymbiosis, and that eukaryotes arose through a symbiotic event entailing a simultaneous endosymbiotic origin of the flagellum and the nucleus, in addition to many other models, which have been reviewed and summarized elsewhere.

The oldest known fossilized prokaryotes were laid down approximately 3.5 billion years ago, only about 1 billion years after the formation of the Earth's crust. Even today, prokaryotes are perhaps the most successful and abundant life-forms.[citation needed] Eukaryotes only appear in the fossil record later, and may have formed from endosymbiosis of multiple prokaryote ancestors. The oldest known fossil eukaryotes are about 1.7 billion years old. However, some genetic evidence suggests eukaryotes appeared as early as 3 billion years ago.

Spirochaetes (also spelled spirochetes)

Spirochaetes (also spelled spirochetes) belong to a phylum of distinctive diderm (double-membrane) bacteria, most of which have long, helically coiled (spiral-shaped) cells. Spirochaetes are chemoheterotrophic in nature, with lengths between 5 and 250 µm and diameters around 0.1–0.6 µm.[citation needed]

Spirochaete

Spirochaetes are distinguished from other bacterial phyla by the location of their flagella, sometimes called axial filaments, which run lengthwise between the bacterial inner membrane and outer membrane in periplasmic space. These cause a twisting motion which allows the spirochaete to move about. When reproducing, a spirochaete will undergo asexual transverse binary fission.

Most spirochaetes are free-living and anaerobic, but there are

Deoxygenated fetal blood passes

Fetoplacental circulation 

Deoxygenated fetal blood passes through umbilical arteries to the placenta. At the junction of umbilical cord and placenta, the umbilical arteries branch radially to form chorionic arteries. Chorionic arteries, in turn, branch into cotyledon arteries. In the villi, these vessels eventually branch to form an extensive arterio-capillary-venous system, bringing the fetal blood extremely close to the maternal blood; but no intermingling of fetal and maternal blood occurs ("placental barrier").

Endothelin and prostanoids cause vasoconstriction in placental arteries, while nitric oxide vasodilation. On the other hand, there is no neural vascular regulation, and catecholamines have only little effect.

cultured cells

 Among the common manipulations carried out on culture cells are media changes, passaging cells, and transfecting cells. These are generally performed using tissue culture methods that rely on sterile technique. Sterile technique aims to avoid contamination with bacteria, yeast, or other cell lines. Manipulations are typically carried out in a biosafety hood or laminar flow cabinet to exclude contaminating micro-organisms. Antibiotics (e.g. penicillin and streptomycin) and antifungals (e.g.amphotericin B) can also be added to the growth media.

   As cells undergo metabolic processes, acid is produced and the pH decreases. Often, a pH indicator is added to the medium to measure nutrient depletion.

Important Type Of stem cells

Importance Of stem cells | Important Type Of stem cells

• Embryonic stem cells
• Adult stem cells
• Hematopoietic stem cell 
• Endothelial stem cell,
• Dental pulp stem cell
• Pluripotent stem cell

transplantation of multipotent hematopoietic stem cells

 Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It is a medical procedure in the fields of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease is a major complication of allogenic HSCT.

  Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As the survival of the procedure increases, its use has expanded beyond cancer, such as autoimmune diseases.

Chondrocyte terminally-differentiate

Chondrocyte terminally-differentiate

From least- to terminally-differentiated, the chondrocytic lineage is:

1. Colony-forming unit-fibroblast (CFU-F)
2. Mesenchymal stem cell / marrow stromal cell (MSC)
3. Chondrocyte
4. Hypertrophic chondrocyte

When referring to bone or cartilage, mesenchymal stem cell (mesoderm origin) are undifferentiated meaning they can differentiate into different variance of generative cells (MSC) are commonly known as osteochondrogenic (or osteogenic, chondrogenic, osteoprogenitor, etc.) cell. Undifferentiated mesenchymal stem cell lose their process, proliferate and crowd together in a dense aggregate of chondrogenic cells(cartilage) at the center of chondrification. These chondrogenic cells will then differentiate to chondroblasts which will then to synthesize the cartilage ECM (extra cellular matrix). Which consists of ground substance(proteoglycans, glycosaminoglycans for low osmotic potential) and fibers. The chondroblasts then trap themselves in a small space that is no longer in contact with the newly created matrix called lacunae which contain extracellular fluid. The chondroblast is now a chondrocyte, which is usually inactive but can still secrete and degrade matrix depending on the conditions. The majority of the cartilage that has been built has been synthesized from the chondroblast which are much more inactive at a late age (adult hood) compared to earlier years (pre-pubesence)

BMP4 and FGF2 have been experimentally shown to increase chondrocyte differentiation.

Chondrocytes undergo terminal differentiation when they become hypertrophic during endochondral ossification. This last stage is characterized by major phenotypic changes in the cell.

Gallery

observations Of Hematopoietic stem cell

observations Of Hematopoietic stem cell

A study involving 2408 donors (18–60 years) indicated that bone pain (primarily back and hips) as a result of filgrastim treatment is observed in 80% of donors by day 4 post-injection. This pain responded to acetaminophen or ibuprofen in 65% of donors and was characterized as mild to moderate in 80% of donors and severe in 10%. Bone pain receded post-donation to 26% of patients 2 days post-donation, 6% of patients one week post-donation, and <2% 1 year post-donation. Donation is not recommended for those with a history of back pain. Other symptoms observed in more than 40% of donors include myalgia, headache, fatigue, and insomnia. These symptoms all returned to baseline 1 month post-donation, except for some cases of persistent fatigue in 3% of donors.  In one metastudy that incorporated data from 377 donors, 44% of patients reported having adverse side effects after peripheral blood HSCT. Side effects included pain prior to the collection procedure as a result of GCSF injections, post-procedural generalized skeletal pain, fatigue and reduced energy.

Severe reactions Of Hematopoietic stem cell

A study that surveyed 2408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6%), although none of these events were fatal. Donors were not observed to have higher than normal rates of cancer with up to 4–8 years of follow up. One study based on a survey of medical teams covered approximately 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about 1 in 1500. This study reported a cardiovascular-related fatality risk within the first 30 days HSCT of about 2 in 10000. For this same group, severe cardiovascular events were observed with a rate of about 1 in 1500. The most common severe adverse reactions were pulmonary edema/deep vein thrombosis, splenic rupture, and myocardial infarction. Haematological malignancy induction was comparable to that observed in the general population, with only 15 reported cases within 4 years.

At the end of 2010, 14.9 million people had registered their willingness to be a bone marrow donor

Donor registration and recruitment

At the end of 2010, 14.9 million people had registered their willingness to be a bone marrow donor with one of the 64 registries from 45 countries participating in Bone Marrow Donors Worldwide. 12.2 million of these registered donors had been ABDR typed, allowing easy matching. A further 453,000 cord blood units had been received by one of 44 cord blood units from 26 countries participating. The highest total number of bone marrow donors registered were those from the USA (6.4 million), and the highest number per capita were those from Cyprus (10.6% of the population).

Within the United States, racial minority groups are the least likely to be registered and therefore the least likely to find a potentially life-saving match. In 1990, only six African-Americans were able to find a bone marrow match, and all six had common European genetic signatures.

Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in South Africa, and a new program is beginning in Nigeria.

Two Types of Hematopoietic stem cell transplantation

Two Types of Hematopoietic stem cell transplantation

 

 

 

 

 

 

 

 

 

 

 

There Are Two Type

1. HIV
2. Multiple sclerosis

 

acute HIV infection

In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the Δ32 deletion. One of the men has been followed for two years and the other for three and a half years. While both are still on HIV treatment, neither shows traces of HIV in their blood plasma and purified CD4 T cells using a sensitive culture method (less than 3 copies/ml). They are also showing a significant decline in HIV antibodies, suggesting a lack of HIV replication.[verification needed]

HIV in their blood plasma and purified CD4 T cells using a sensitive culture method

In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the Δ32 deletion. One of the men has been followed for two years and the other for three and a half years. While both are still on HIV treatment, neither shows traces of HIV in their blood plasma and purified CD4 T cells using a sensitive culture method (less than 3 copies/ml). They are also showing a significant decline in HIV antibodies, suggesting a lack of HIV replication.[49][verification needed]In 2007, a team of doctors in Berlin, Germany, including Gero Hütter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive. From 60 matching donors, they selected a [CCR5]-Δ32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations..The transplant was repeated a year later after a relapse. Over three years after the initial transplant and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies. Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case.[46] Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.

stem cell transplant for leukemia patient Timothy Ray Brown

In 2007, a team of doctors in Berlin, Germany, including Gero Hütter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive. From 60 matching donors, they selected a [CCR5]-Δ32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations. The transplant was repeated a year later after a relapse. Over three years after the initial transplant and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies.. Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case. Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.

HIV entry to T cell

In 2007, a team of doctors in Berlin, Germany, including Gero Hütter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive. From 60 matching donors, they selected a [CCR5]-Δ32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations. The transplant was repeated a year later after a relapse. Over three years after the initial transplant and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies.. Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case. Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.

Hematopoietic stem cell McAllister's 1997

  Hematopoietic stem cell McAllister's 1997

Since McAllister's 1997 report on a patient with multiple sclerosis (MS) who received a bone marrow transplant for CML, there have been over 600 reports of HSCTs performed primarily for MS. These have been shown to "reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients" that have aggressive highly active multiple sclerosis, "in the absence of chronic treatment with disease-modifying agents".

endothelial cells (ECs) endothelium that lines the inner surface of blood vessels

ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. These parent stem cells, ESCs, give rise to progenitor cells, which are intermediate stem cells that lose potency. Progenitor stem cells are committed to differentiating along a particular cell developmental pathway. ESCs will eventually produce endothelial cells (ECs), which create the thin-walled endothelium that lines the inner surface of blood vessels and lymphatic vessels.

1)  Sources

2) Properties

2.1 Self-renewal and differentiation

2.2 Blood vessel formation

2.3 Markers

3) Role in formation of vascular system

4) Role of insulin-like growth factors in endothelium     differentiation

5) Animal models of vasculogenesis

6) Role in recovery

7) Role in cancer

8)Future efforts

ESCs Endothelial stem cells

Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types.

histological analysis Endothelium Stem Cell

histological analysis Endothelium Stem Cell

ECs were first thought to arise from extraembryonic tissues because blood vessels were observed in the avian and mammalian embryos. However, after histological analysis, it was seen that ECs were in the embryo. This meant that blood vessels come from an intraembryonic source, the mesoderm.

G2 phase DNA synthesis and mitosis

G2 phase DNA synthesis and mitosis

During the gap between DNA synthesis and mitosis, the cell will continue to grow. The G2 checkpoint control mechanism ensures that everything is ready to enter the M (mitosis) phase and divides

The process of mitosis is complex and highly regulated "M phase".

The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase and telophase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatidsto opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.

Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "M phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei in a process called endoreplication. This occurs most notably among the fungi and slime moulds, but is found in various groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development.[6] Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.

cell separates the chromosomes in its cell nucleus Prokaryotic cells

  Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly equal shares of these cellular components. Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle - the division of the mother cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 10% of the cell cycle.

Mitosis occurs exclusively in eukaryotic cells, but occurs in different ways in different species. For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces cerevisiae (yeast) undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus. Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.

nuclear division psychokinesis

nuclear division (psychokinesis)

The relatively brief M phase consists of nuclear division (karyokinesis). The M phase has been broken down into several distinct phases, sequentially known as : 

• prophase,
• metaphase,
• anaphase,
• telophase
• cytokinesis

cell-division cycle

The cell cycle, or cell-division cycle, is the series of events that take place in a cell leading to its division and duplication (replication). In cells without a nucleus (prokaryotic), the cell cycle occurs via a process termed binary fission. In cells with a nucleus (eukaryotes), the cell cycle can be divided in two periods: interphase—during which the cell grows,        accumulating nutrients needed for mitosis and duplicating its DNA—and the mitotic (M) phase, during which the cell splits itself into two distinct cells, often called "daughter cells" and the final phase, cytokinesis, where the new cell is completely divided. The cell-division cycle is a vital process by which a single-celled fertilized egg develops into a mature organism, as well as the process by which hair, skin, blood cells, and some internal organs are renewed.

G1 cyclin-CDK complexes

G1 cyclin-CDK complexes

  Upon receiving a pro-mitotic extracellular signal, G1 cyclin-CDK complexes become active to prepare the cell for S phase, promoting the expression of transcription factors that in turn promote the expression of S cyclins and of enzymes required for DNA replication. The G1 cyclin-CDK complexes also promote the degradation of molecules that function as S phase inhibitors by targeting them for ubiquitination. Once a protein has been ubiquitinated, it is targeted for proteolytic degradation by the proteasome.
   Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes assembled during G1 phase on DNA replication origins. The phosphorylation serves two purposes: to activate each already-assembled pre-replication complex, and to prevent new complexes from forming. This ensures that every portion of the cell's genome will be replicated once and only once. The reason for prevention of gaps in replication is fairly clear, because daughter cells that are missing all or part of crucial genes will die. However, for reasons related to gene copy number effects, possession of extra copies of certain genes is also deleterious to the daughter cells.
   Mitotic cyclin-CDK complexes, which are synthesized but inactivated during S and G2 phases, promote the initiation of mitosis by stimulating downstream proteins involved in chromosome condensation and mitotic spindle assembly. A critical complex activated during this process is a ubiquitin ligase known as the anaphase-promoting complex (APC), which promotes degradation of structural proteins associated with the chromosomal kinetochore. APC also targets the mitotic cyclins for degradation, ensuring that telophase and cytokinesis can proceed.

Cyclin D-CDK4 complex

    Cyclin D is the first cyclin produced in the cell cycle, in response to extracellular signals (e.g. growth factors). Cyclin D binds to existing CDK4, forming the active cyclin D-CDK4 complex. Cyclin D-CDK4 complex in turn phosphorylates the retinoblastoma susceptibility protein (Rb).
       The hyperphosphorylated Rb dissociates from the E2F/DP1/Rb complex (which was bound to the E2F responsive genes, effectively "blocking" them from transcription), activating E2F. Activation of E2F results in transcription of various genes like cyclin E, cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which pushes the cell from G1 to S phase (G1/S , which initiates the G2/M transition. Cyclin B-cdc2 complex activation causes breakdown of nuclear envelope and initiation of prophase, and subsequently, its deactivation causes the cell to exit mitosis.

The genes p21, p27 and p57

   The genes p21, p27 and p57

Two families of genes, the cip/kip family (CDK interacting protein/Kinase inhibitory protein) and the INK4a/ARF (Inhibitor of Kinase 4/Alternative Reading Frame) prevent the progression of the cell cycle. Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors.
   The cip/kip family includes the genes p21, p27 and p57. They halt cell cycle in G1 phase, by binding to, and inactivating, cyclin-CDK complexes. p21 is activated by p53 (which, in turn, is triggered by DNA damage e.g. due to radiation). p27 is activated by   Transforming Growth Factor of β (TGF β), a growth inhibitor.
The INK4a/ARF family includes p16INK4a, which binds to CDK4 and arrests the cell cycle in G1 phase, and p19ARF which prevents p53 degradation.
   Synthetic inhibitors of Cdc25 could also be useful for the arrest of cell cycle and therefore be useful as antineoplastic and anticancer agents.

Inhibitor of Kinase 4/Alternative Reading Frame

Inhibitor of Kinase 4/Alternative Reading Frame

   Two families of genes, the cip/kip family (CDK interacting protein/Kinase inhibitory protein) and the INK4a/ARF (Inhibitor of Kinase 4/Alternative Reading Frame) prevent the progression of the cell cycle. Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors.
   The cip/kip family includes the genes p21, p27 and p57. They halt cell cycle in G1 phase, by binding to, and inactivating, cyclin-CDK complexes. p21 is activated by p53 (which, in turn, is triggered by DNA damage e.g. due to radiation). p27 is activated by   Transforming Growth Factor of β (TGF β), a growth inhibitor.
The INK4a/ARF family includes p16INK4a, which binds to CDK4 and arrests the cell cycle in G1 phase, and p19ARF which prevents p53 degradation.
   Synthetic inhibitors of Cdc25 could also be useful for the arrest of cell cycle and therefore be useful as antineoplastic and anticancer agents.

CDK-cyclin machinery cell cycle

 

Evidence suggests that a semi-autonomous transcriptional network acts in concert with the CDK-cyclin machinery to regulate the cell cycle. Several gene expression studies in Saccharomyces cerevisiae have identified approximately 800 to 1200 genes that change expression over the course of the cell cycle. They are transcribed at high levels at specific points in the cell cycle, and remain at lower levels throughout the rest of the cell cycle. While the set of identified genes differs between studies due to the computational methods and criterion used to identify them, each study indicates that a large portion of yeast genes are temporally regulated.
    Many periodically expressed genes are driven by transcription factors that are also periodically expressed. One screen of single-gene knockouts identified 48 transcription factors (about 20% of all non-essential transcription factors) that show cell cycle progression defects. Genome-wide studies using high throughput technologies have identified the transcription factors that bind to the promoters of yeast genes, and correlating these findings with temporal expression patterns have allowed the identification of transcription factors that drive phase-specific gene expression. The expression profiles of these transcription factors are driven by the transcription factors that peak in the prior phase, and computational models have shown that a CDK-autonomous network of these transcription factors is sufficient to produce steady-state oscillations in gene expression).
    Experimental evidence also suggests that gene expression can oscillate with the period seen in dividing wild-type cells independently of the CDK machinery. Orlando et al. used microarrays to measure the expression of a set of 1,271 genes that they identified as periodic in both wild type cells and cells lacking all S-phase and mitotic cyclins (clb1,2,3,4,5,6). Of the 1,271 genes assayed, 882 continued to be expressed in the cyclin-deficient cells at the same time as in the wild type cells, despite the fact that the cyclin-deficient cells arrest at the border between G1 and S phase. However, 833 of the genes assayed changed behavior between the wild type and mutant cells, indicating that these genes are likely directly or indirectly regulated by the CDK-cyclin machinery. Some genes that continued to be expressed on time in the mutant cells were also expressed at different levels in the mutant and wild type cells. These findings suggest that while the transcriptional network may oscillate independently of the CDK-cyclin oscillator, they are coupled in a manner that requires both to ensure the proper timing of cell cycle events. Other work indicates that phosphorylation, a post-translational modification, of cell cycle transcription factors by Cdk1 may alter the localization or activity of the transcription factors in order to tightly control timing of target genes (Ubersax et al. 2003; Sidorova et al. 1995; White et al. 2009).
    While oscillatory transcription plays a key role in the progression of the yeast cell cycle, the CDK-cyclin machinery operates independently in the early embryonic cell cycle. Before the midblastula transition, zygotic transcription does not occur and all needed proteins, such as the B-type cyclins, are translated from maternally loaded mRNA.

Role in tumor formation

Role in tumor formation 

  A dis regulation of the cell cycle components may lead to tumor formation. As mentioned above, some genes like the cell cycle inhibitors, RB, p53 etc., when they mutate, may cause the cell to multiply uncontrollably, forming a tumor. Although the duration of cell cycle in tumor cells is equal to or longer than that of normal cell cycle, the proportion of cells that are in active cell division (versus quiescent cells in G0 phase) in tumors is much higher than that in normal tissue. Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same.
    The cells which are actively undergoing cell cycle are targeted in cancer therapy as the DNA is relatively exposed during cell division and hence susceptible to damage by drugs or radiation. This fact is made use of in cancer treatment; by a process known as debunking, a significant mass of the tumor is removed which pushes a significant number of the remaining tumor cells from G0 to G1 phase (due to increased availability of nutrients, oxygen, growth factors etc.). Radiation or chemotherapy following the debunking procedure kills these cells which have newly entered the cell cycle.[
    The fastest cycling mammalian cells in culture, crypt cells in the intestinal epithelium, have a cycle time as short as 9 to 10 hours. Stem cells in resting mouse skin may have a cycle time of more than 200 hours. Most of this difference is due to the varying length of G1, the most variable phase of the cycle. M and S do not vary much. In general, cells are most radio sensitive in late M and G2 phases and most resistant in late S.
     For cells with a longer cell cycle time and a significantly long G1 phase, there is a second peak of resistance late in G1.
The pattern of resistance and sensitivity correlates with the level of sulfhydryl compounds in the cell. Hydrofoils are natural radioprotectors and tend to be at their highest levels in S and at their lowest near mitosis.