Monday, April 14, 2008

Dow Jones Industrial Index Will Test Previous Trough Support

Mid Bolinger Band support was taken out on Friday and next support will be the previous trough at 12176.10 indicated by the green dash line. Watch for possible short term rebounce at this level on volatile trading on Monday. Closing below this level will increase bearish momentum and will result in a test of the black dotted support line at around 11800.

Cosco 5 mins chart 14 Apr 2008 1521 hrs

Intraday uptrend has formed after rebounce from low of $2.79 this morning. Key resistances are at $3.00 and $2.96 which is near the 200 EMA resistance line. Key support band is $2.87 to $2.85 followed by $2.82 to $2.79 the current day low. Monitor 20 and 50 EMA support lines.

promise of stem cells

Much of the promise of stem cells rests on a scheme for replacing parts worn out by age, injury, or infirmity. Unfortunately, the reality of stem cell biology is overshadowed by the hype. For example, the future is imagined to hold an inexhaustible source of stem cells with a perfect genetic match banked at a local hospital, available for your every medical whim. Need a new pancreas? Place your order, and three weeks later a new one lies ready and waiting in the surgical suite. Heart failure? No worries -- a few injections with multipotent stem cells will grow new cardiac tissue. And thus may 21st century patients extend their lives -- through a kind of patchwork medicine, held together by a fabulous, potent cell. This future sounds incredibly exciting. But it will take time -- and vision -- to us get there.

The truth of the matter is, we've got a goodly distance to go before regenerative medicine -- a catchall term for stem cell therapy -- will help large numbers of patients. It is very possible that many diseases will have to wait for cures from other quarters of medicine. Before any medical treatment (including cell and tissue transplants) is made available through hospitals or clinics, it must first be tested in humans through tightly regulated phases of clinical trials. The first phase determines safety and side effects in a few dozen subjects; the second phase tests efficacy in hundreds of patients; the third and subsequent phases try to prove statistical significance and confirm its effects in many hundreds or thousands of patients. The U.S. Food and Drug Administration (FDA) evaluates the data, and if the results pass muster, the product is approved for sale and moves to the market. Developing a new therapy goes slowly and is terribly expensive -- discovering, testing, and manufacturing one new drug can take between 10 and 15 years and cost nearly a billion dollars.

A hypothetical timeline of a new treatment for skin transplants might look like this:

• Basic Research: In 2006, a source of powerful adult stem cells is discovered beneath human skin. The rare cells are fingerprinted by genetic markers, and the markers are used to isolate the cells from the body and culture them in the lab. Over the next two years, technology is developed to grow the cells in quantity and used to change them into a variety of skin cell types.

• Preclinical Research: Different lines of skin stem cells and their progenitors are transplanted into the injured skin of a transgenic mouse with no immune system (to prevent rejection of the human cells). Over time the transplants are observed. One line works: the cells survive, go to the site of the injury, integrate into the skin, and heal the wound. Other kinds of animals are similarly tested. The tests take three years to complete.

• Clinical Research: The encouraging results in animals prompt tests in humans. In patients with severe burns, the patient's own skin stem cells are cultured, multiplied and then transplanted at the wound site. The cells improve blood flow, promote healing, and reduce scarring. Using adult stem cells is not the only way to approach the problem. An hESC line using nuclear transfer might also produce the skin stem cell in question. The technologies are further developed by companies, tested in more humans, and manufactured for use for burn victims. In 2014, the FDA approves the first cell therapy for use in clinics.

If the treatment being studied is for a disease with a genetic cause, another wrinkle must be ironed out. The faulty gene has to be corrected before the cells are reintroduced or the transplant could succumb with time, as did the original cells. This presents an added set of challenges to stem cell transplants. Once a genetically engineered stem cell is placed into the body and grafts into an organ, it may be there for life. If the change is in one of the wide-ranging cells of the blood or nervous system, the proteins made by the new gene will be everywhere in the body. Care must be taken to limit the effects of the therapy only to the affected areas.

What are the unique properties of all stem cells?

Stem cells differ from other kinds of cells in the body. All stem cells—regardless of their source—have three general properties: they are capable of dividing and renewing themselves for long periods; they are unspecialized; and they can give rise to specialized cell types.

Scientists are trying to understand two fundamental properties of stem cells that relate to their long-term self-renewal:

  1. why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot; and
  2. what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal?

Discovering the answers to these questions may make it possible to understand how cell proliferation is regulated during normal embryonic development or during the abnormal cell division that leads to cancer. Importantly, such information would enable scientists to grow embryonic and adult stem cells more efficiently in the laboratory.

Stem cells are unspecialized. One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell); and it cannot fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell). However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells.

Stem cells are capable of dividing and renewing themselves for long periods. Unlike muscle cells, blood cells, or nerve cells—which do not normally replicate themselves—stem cells may replicate many times. When cells replicate themselves many times over it is called proliferation. A starting population of stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal.

The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to grow stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took 20 years to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. Therefore, an important area of research is understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed for repair of a specific tissue. Such information is critical for scientists to be able to grow large numbers of unspecialized stem cells in the laboratory for further experimentation.

Stem cells can give rise to specialized cells. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. Scientists are just beginning to understand the signals inside and outside cells that trigger stem cell differentiation. The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA, and carry coded instructions for all the structures and functions of a cell. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment.

Therefore, many questions about stem cell differentiation remain. For example, are the internal and external signals for cell differentiation similar for all kinds of stem cells? Can specific sets of signals be identified that promote differentiation into specific cell types? Addressing these questions is critical because the answers may lead scientists to find new ways of controlling stem cell differentiation in the laboratory, thereby growing cells or tissues that can be used for specific purposes including cell-based therapies.

Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a blood-forming cell in the bone marrow—which is called a hematopoietic stem cell—could not give rise to the cells of a very different tissue, such as nerve cells in the brain. However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue, a phenomenon known as plasticity. Examples of such plasticity include blood cells becoming neurons, liver cells that can be made to produce insulin, and hematopoietic stem cells that can develop into heart muscle. Therefore, exploring the possibility of using adult stem cells for cell-based therapies has become a very active area of investigation by researchers.

Impact of embryonic and adult stem cells on the future of medicine and health care

Stem cell therapy is not a conventional treatment using an external agent and so the normal 15 year development pipeline for new pharmaceutical products does not apply. Indeed the gap between seeing promising stem cell results in animals and starting first human trials can be as short as 15 days.

Suppose you have a heart attack. A cardiothoracic surgeon talks to you about using your own stem cells in an experimental treatment. You agree. A sample of bone marrow is taken from your hips, and processed using standard equipment found in most oncology centers for treating leukemia. The result is a concentrated number of special bone marrow cells, which are then injected back into your own body - either into a vein in your arm, or perhaps direct into the heart itself.

The surgeon is returning your own unaltered stem cells back to you, to whom these cells legally belong. This is not a new molecule requiring years of animal and clinical tests. Your own adult stem cells are available right now. No factory is involved - nor any pharmaceutical company sales team.

What is more, there are no ethical questions (unlike embryonic stem cells), no risk of tissue rejection, no risk of cancer.

Now we begin to see why research funds are moving so fast from embryonic stem cells to adult alternatives.

Harvard Medical School is another center of astonishing progress in adult stem cells. Trials have shown partially restored sight in animals with retinal damage. Clinical trials are expected within five years, using adult stem cells as a treatment to cure blindness caused by macular degeneration - old-age blindness and the commonest cause of sight-loss in America. Within 10 years it is hoped that people will be able to be treated routinely with their own stem cells in a clinic using a two-hour process.

If you want further evidence of this switch in interest from embryonic to adult stem cells,, look at the makers of Dolly the sheep. The Rosslyn Institute in Scotland are pioneers in cloning technology. They along with others campaigned successfully in UK Parliament for the legal right to use the same technology in human embryos (therapeutic cloning, not with the aim of clones being born). But three years later, they had not even bothered to apply for a human cloning licence.

Why not? Because investors were worried about throwing money at speculative embryo research with massive ethical and reputational risks. Newcastle University made headlines in August 2004 when granted the first licence to clone human embryos - but the real story was why it had taken so long to get a single research institute in the UK to actually get on and apply. Answer: medical research moved on and left the "therapeutic" human cloners behind.

Properties of stem cells

The classical definition of a stem cell requires that it possess two properties:

  • Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
  • Potency - the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent - to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells.

Potency definitions

Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Pluripotent, embryonic stem cells originate as inner mass cells within a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.

  • Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
  • Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
  • Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
  • Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells (e.g. muscle stem cells).

Identifying stem cells

The practical definition of a stem cell is the functional definition - the ability to regenerate tissue over a lifetime. For example, the gold standard test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. 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, where single cells are characterized by their ability to differentiate and self-renew.[4][5] As well, stem cells can be isolated based on a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.

Germany relaxs limits on stem cell research

Germany has decided to ease restrictions on stem cell research to ensure its scientists stay ahead of the pack.

The Bundestag lower house of parliament has approved new measures amid fears the country's top scientists would move abroad if rules remained too restrictive.

Under the bill, researchers will now be able to import stem cells created before the first of May 2007, rather than only use cells existing before 2002.

But the new limits were only passed after an emotionally charged debate.

Technology and Research Minister, Annette Schavan, stressed that scientists would be able to extract stem cells out of embryos that are not destined for a pregnancy.

She also said that Germany had to ensure its scientists could keep up globally.

Many of those who believe that life begins at conception argued that cells should be harvested from adults, not embryos.

German lawmakers also voted against two more radical proposals - one calling for a ban on all embryonic stem cell research, the other suggesting the cut-off date be scrapped entirely.