February 16, 2009

Stem Cells: the basic

Today I begin a short discussion about Stem Cells. How you know, this is a very actual and controversial theme with many implication in medicine. We will start with some definitions and general principles. Of course, this is a special paper for a blog and it will be incomplete but not superficial due that every day we have new information in this field. I hope enjoy these short essays.

FACT 1: What are pluripotent stem cells?
The stem cells are cells capable of sustaining unlimited division cycles indefinitely perpetuating the same original style but with ability to differentiate, become a stem or trunk, and become one of the 200 specialized cell varieties and cease its divisions. They are the normal reservoir of new cells that are necessary to replace damaged or dead. Retain the capacity to multiply as such to be required, which will culminate in its differentiation of cells in tissue repair. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. Stem cells have two important characteristics that distinguish them from other types of cells.
First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become specialized cells with special functions such as the beating cells of the heart muscle or the insulin producing cells of the pancreas. Scientists are trying to understand two fundamental properties of stem cells that relate to their long term self-renewal: a) why can embryonic stem cells proliferate for a year or more in the laboratory without differentiating, but most adult stem cells cannot; and b) what are the factors in living organisms that normally regulate stem cell proliferation and self-renewal.

FACT 2: Origin of stem cells
Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics. They discovered ways to obtain or derive stem cells from early mouse embryos more than 20 years ago. Many years of detailed study of the biology of mouse stem cells led to the discovery. In 1998, they isolated stem cells from human embryos and grow the cells in the laboratory. These were called human embryonic stem cells. The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
Adult stem cells are now call adult progenitor stem cells. Those who lack a population of stem cells/progenitor throughout life will not be able to self-repair. Not even explain the reason why some bodies and others have no such cell populations. The tissues are deficient in them, mainly the brain, heart, spinal cord, eye and kidney. They have an important role in the regeneration process would be fired induced by implanted stem cells, in which case it opens another line: the search for the factors that trigger or induce such a response in quality and/or greater than the usual amount to disease or tissue damage.
Much has been speculated about the type of cell in which you can become a progenitor mononuclear cell in adult stage, if only give rise to another cell or tissue from which most of any other tissue from the same embryological layer. One example is the renovation or replacement of spare cells in the blood. Bleeding or donation to stimulate stem cells in bone marrow cells needed to create, passing several stages of differentiation, followed by separation of such stem cells. The difference between stem cells and bone marrow that are differentiating into blood cells is the loss of their ability to divide, which can be done during certain stages, but not in others. The cells do not fully mature but directed toward a specific type of differentiation, called precursors or progenitors, rather than stem cells, accepting that the subtle difference between them is not always so clear.
See: Culture of Mouse Neural Stem Cell Precursors

FACT 3: Stem cells from fetal tissues
At approximately 12 weeks of gestation primitive bodies are formed and their final location. Over the next 6 months, they have increased in size and develop the ability to operate independently of the placenta. As the fetus grows very quickly, all the tissues and organs, including brain contains stem cells, which aroused the interest of researchers and society concerned about the possible tampering with them. From three sources: trophoblast, primitive germ cells and fetal tissues.
As with many other cell types, the trophoblast cells can auto perpetuate and scientist were unable to prevent their differentiation. It seems to be happening with all the stem cells, at least in laboratory cultures, continually divide and differentiate, suggesting that such differentiation is the process that occurs by default, which means a natural limit to the size of organs and a barrier to tumor formation. If so, the environment that supports such a state of lack of differentiation, should express the genes whose products inhibit.
In tissues, in addition, the medium must also inhibit cell division unless new cells are needed. An essential contribution was made by Janet Rossant in Toronto, to find that the fibroblast growth factor 4 (FGF4) using heparin as a co-factor was as necessary as the layers of fibroblasts nutrients to keep in trophoblast undifferentiated stem cells. The injection of these cells in the blastocyst produced only trophoblastic tissue. Other stem cells that aroused great interest are the embryonic or fetal-fetal cells. Researchers have to get parental approval for donations of fetal tissues between 5 and 12 weeks of gestation, according to the legislation in most of the countries where the harvesting of them is authorized and regulated. The window of 5-12 weeks is advantageous because until the 5th week almost all cells are stem cells with almost no degree of differentiation and high mitotic rate that can generate Teratomas. From 12 weeks, the immune system HLA (Human Antigen Leukocyte) is already developed and the implantation of stem cells can cause immune rejection in the receiver.

FACT 4: Embryonic stem cells.
Before organogenesis, the embryo of any species is a compressed collection of cells with the potential to become any organ or tissue, which are called pluripotent. First described in mice in the laboratory is relentless and infinitely divided and maintain the ability to differentiate into any cell type when exposed to the proper growth factor, such as the formation of nerves can transmit electrical and chemical signals, similar to the body. Here comes the enthusiasm to develop regenerative therapies in Parkinson, Alzheimer, spinal injuries and degenerative diseases of retina. They are undoubtedly the most pluripotent of all, have the greatest therapeutic potential. They are immortal and capable of pluripotent differentiationl. Chromosomal composition remains stable over many cell cycles. Jobs in USA, Australia and Israel are giving rise to cells of the three embryonic layers. Them were injected into immune suppressed mice and they originated Teratomas with intestinal epithelial cells (endoderm), striated and smooth muscle (mesoderm) and squamous epithelium (ectoderm).
See: Propagation of Embryonic Stem Cells

FACT 5: Stem cells by parthenogenesis.
This process so far only achieved in primates and an experimental basis. This is the artificial activation of an egg without having been fertilized by changes in flow of calcium. The cell line had the same feature from other embryonic stem cells: normal chromosomes, capable of endless cycles of growth and division, contain significant amounts of telomerase, which is thought to play a fundamental role in the maintenance of the integrity of chromosomes through successive divisions and had allegedly antigens associated with embryonic stem cells. They can become any other race, including dopaminergic neurons. Their pluripotent action has been demonstrated by the appearance of teratomas appropriate models of rats, where the 3 layers of tissue were found: blood vessels, intestines primitive smooth and striated muscle, bone and cartilage. These results suggest that although the eggs activated by this process not give rise to an individual, can theoretically provide pluripotent cells. Many questions and problems with this line have not yet been overcome.
See: Derivation of Human Embryonic Stem Cells by Immunosurgery

FACT 6: Stem cells by nuclear transplantation
Since every cell in the body contains all the chromosomes, each cell of every tissue is a reservoir of all the genes of each individual. The only exception is the mature sperm, which contains only half, with populations of sperm X or Y. It was found that nuclear material (chromosomes) of a cell implanted into an egg may be home to an individual identical to the donor of nuclear material. This is called cloning, Greek clon, or branch line that once planted can cause the same plant. This type of cloning could be used to create stem cells in need of individual, with their own genetic and replacing damaged or lost. The gene replacement therapy could help millions of diabetics, a hemophilic, and so on. Today, it is subject to restrictions for fear that human cloning arouses in some social and religious groups.

FACT 7: How a cell becomes in another?
The mechanisms of action are:
1. Cell differentiation: the process to become a mature cell, not divisible, which specializes in the expression of gene products required to meet tissue specific functions, such as the synthesis of specific proteins from cells also specialize in secretion and driving.
2. Trans-differentiation or plasticity: Conversion of a differentiated cell to another, with or without prior cell division.
3. Metaplasia: Conversion of a cell or tissue type into another.

Trans-differetiation also includes the conversion between undifferentiated stem cells from different tissues. Cell divisions are usually involved but sometimes not, as evidenced by the lack of uptake of 5-BrdU during processing. While there is little evidence of that, has proved attractive to assume that stem cells from a particular tissue in the body like those in its embryonic state. I used to assume that these stem cells are predetermined to form cell types that just tissue, but is not that simple. Several studies have postulated that the stem cells are so complex as to have plastic behavior depending on the environment in which they are highly sensitive to signals emanating from damaged tissues. The transplantation of bone marrow cells was the first demonstration of a cell type that can cause another. It was found the formation of muscle from bone marrow harvested from transgenic mice in which the promoter 3F of myosin light chain was used to guide the expression of nuclear beta-galactosidase. They took bone marrow of this strain and is injected into immunosuppressed mice to whom myonecrosis caused by chemical cardiotoxin. In bone marrow there is no expression of beta-galactosidase but was activated in cells that became associated with the muscle of the host. Although trans-diffrentiation happened, it was much slower (months) caused by the resident satellite cells, which became in muscle in a period of days. This time difference indicates that metaplasia from muscle to bone marrow could be a multi-step process that involves migration, differentiation and possibly final determination. Other researchers also differentiated tissues derived from cells of bone marrow.

FACT 8: Clinical and therapeutic uses
Research on stem cells is advancing knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often referred to as regenerative or reparative medicine. Stem cells are one of the most fascinating areas of biology today. But like many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.
Countless diseases and functional deficiencies seem likely to be treated with stem cells. Diabetes, liver cirrhosis, arthritis, neurological diseases (Alzheimer, Parkinson), spinal cord injuries, ischemic or idiopathic dilated cardiomyopathies, acute myocardial infarction, anemia, leukemia, finally, have been treated with this method and others (kidney failure, some types of cancer, etc..) are currently being studied. Obviously there is a tendency to get a cell lineage with enough potential to regenerate tissues needed, stored and available for immediate use. We will discuss these issues in detail further.

Where can I get more information?
For a more detailed discussion of stem cells, see the following Web sites:
http://www.news.wisc.edu/packages/stemcells/ The University of Wisconsin's Web site about stem cells, written for general audiences.
http://www.eurekalert.org/ EurekAlert! is a publicly accessible science news site run by the American Association for the Advancement of Sciences. Search for "stem cells."
http://scitechdaily.com/ A site that offers a range of news articles, features, and commentaries about science and technology topics. Search for "stem cells."
http://www.sciam.com/ The Web site for Scientific American. Search for "stem cells."
http://www.reuters.com/newsChannel.jhtml?type=scienceNews The Reuters news site for stories about science. Search for "stem cells" and select "News and Pictures."
http://www.stemcellresearchnews.com/ A commercial, online newsletter that features stories about stem cells of all types.

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