Anatomy 101: Stem Cells

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Stem Cell Characteristics

A stem cell is defined by two characteristics:

  1. it has the ability to self renew, that is make exact copies of itself, through a process of cell division; and
  2. it has the ability to develop into many different types of mature cells. One stem cell, from whatever source, adult or embryo, can generate thousands and thousands of exact copies.



Where Human Embryonic Stem Cells Come From

Stem cells are derived from blastocysts that are left over after couples have had children using in vitro fertilization. For couples using in vitro fertilization, the woman has eggs harvested, which are then fertilized by sperm in a dish in the clinic. Eggs that are successfully fertilized are allowed to divide for 3-6 days, forming tiny balls of a 100 or so cells called blastocysts. These are frozen, and when the couple is ready, a few of these are implanted in the woman's womb.


"Embryonic" stem cells is actually a misnomer. These cells come from blastocysts. which are developmentally younger than embryos.

After the couple has conceived, they must decide what to do with the left over blastocysts. Some couples pay to keep their remaining blastocysts frozen, but most left over blastocysts are simply discarded! These discarded blastocysts, numbering in the hundreds of thousands, could be used to derive stem cells. The lines that are approved by the Federal government were created when couples donated their unwanted frozen embryos to research.

The blastocysts are like tennis balls, solid on the outside, but hollow in the middle. Stem cells are found in a little lump inside that hollow ball. Researchers have found a way to crack the ball in half and remove the stem cells.

Stems cells removed from the hollow ball can never develop into a human. The hollow ball contains the instructions or blue print to create a human from the stem cells. Without the instructions, a human can never form.

Once the stem cells are removed and placed in a dish in the lab, they continue to make exact copies of themselves, called daughter cells. They will only make exact copies of themselves and nothing else until a researcher adds different chemicals, or molecular signals, that tell the stem cells to become something else. Once we understand what makes them become what ever cell type, be it heart, pancreas, liver, or spinal cells, we have exquisite control over the repair process, being able to replace the cell type we want with more of the tissue derived from stem cells.

human embryonic stemcells


Stem Cell Lines

Blastocyst

A stem cell "line" is the family of cells derived from a single original stem cell.

Each of the different embryonic stem cell lines that exist today was derived from an individual human blastocyst (an earlier developmental stage than an embryo, containing about 100 cells). The lines that are designated as "approved" are the ones that existed prior to August 2001, when President Bush announced that federal funds could be used for research on the approximately 70 lines that were thought to exist at that time, but could not be used to study any lines developed subsequently. We now know that only 10-15 of these lines are usable, and there is concern that most of lines may be contaminated as a result of having been grown initially on mouse feeder cells. Since 2001, techniques have been developed that allow the derivation of lines without the use of mouse cells, and so new lines that are developed today would not have the same contamination problem. Also, scientists are already finding that there are differences between the lines, which may limit the usefulness of some of the existing lines for particular applications.

Many scientists believe that cellular transplant therapies will require the kind of genetic matching that is now required for organ transplants in order to avoid "rejection" (the process through which the body attacks and destroys foreign tissue). Because of the genetic diversity of people, it will probably be necessary to develop many different stem cell lines that allow matching between donor cells and recipients.


Somatic Nuclear Transfer (Therapeutic Cloning)

The goal of therapeutic cloning is straightforward, to develop treatments for disease and injury from stem cells that have the same nucleus, and so DNA, as the injured or sick individual. This is done through a process whereby an egg from a donor has its nucleus, housing the genetic material, removed and replaced by the nucleus of the person needing treatment.

The whole process starts with an egg from a donor and a cell, for example a skin cell or a cell scraped from inside the cheek, from the person who requires treatment. The nucleus of the donor egg is gently squeezed out, without damaging the rest of the egg. The same is done with the skin cell, and the nucleus from the skin cell is then inserted deep inside the egg cell, thereby replacing the nucleus with new nucleus. The egg with its new nucleus is exposed to a variety of chemicals and growth factors that induce the cell to divide and develop into a blastocyst. As described above, the blastocyst is cracked open and the stem cells are removed.

The difference between stem cells gathered from a fertilized egg and those gathered from therapeutic cloning is that cloned cells have the DNA of the person who needs treatment; they are patient-specific stem cells. When these cells are transplanted into that person's body, the cells will be recognized as "self." This means that the immune system will not attack the transplant, and there will be no need for life long immunosuppression (see below).

The controversy over therapeutic cloning comes in part from the name cloning, which suggests the cloning of a person, and in part from the fact that reproductive cloning uses the same techniques up to the development of the blastocyst. With therapeutic cloning, the blastocyst is broken apart, and can never develop into a person.

Cloning


Embryonic Stem Cells vs. Adult Stem Cells

embryonic and adult stem cells All stem cells have certain basic characteristics, the ability to make copies of themselves and the ability to turn into other cell types. However, there are two general categories of stem cells, embryonic and adult. By definition, embryonic stem cells are derived from blastocysts (developed during in vitro fertilization and donated to research with permission from the donors). These cells are undifferentiated and pluripotent. Adult stem cells, on the other hand, are undifferentiated cells found in tissue or organs with differentiated cells. These cells are multipotent.

To understand this difference, it helps to understand how cells develop, how they go from being very young cells to mature cells, from undifferentiated to differentiated. Embryonic stem cells are the youngest cells we know of. All the cells in your body started with the 30 or so stem cells that develop 3-6 days after fertilization. Embryonic stem cells are completely undifferentiated. They can turn into almost any cell type in the body; this is called pluripotent.

As a cell matures, it begins to differentiate or head down the path toward a specific cell type. For example, neural stem cells are cells that can self renew, but will only become nervous system cells (that is, a neuron, an astrocyte or an oligodendrocyte). Cell that have a more limited potential are called "multipotent."

The oldest cells are one that are fully differentiated and mature. These cells no longer are able to make copies of themselves, and they will not change their identity.


Immunosuppression

The immune system helps protect the human body from disease and infection. It does this by being able to recognize cells from the body, "self", and cells that are from outside the body, "not-self". For example, when you fall and skin your knee, dirt and debris may enter the wound as well as microorganisms from the environment. Your immune system would detect the dirt and microorganisms as not belonging and would search them out and destroy them.


As with a kidney or liver transplant, people who receive embryonic stem cell therapies will likely need like-long drugs to trick their immune systems into not rejecting the transplanted cells.

There are, however, situations where the normal response of the immune system is a problem. If you require an organ transplant, your immune system will recognize the new organ as "not self" and will try to destroy it. That is why people who receive organ transplants must also be treated with strong drugs that suppress the immune system, called immunosuppressents. Their immune system must be partially or completely shut down to save the transplant from being attacked and destroyed. Immunosuppression is not without danger. When the immune system is impaired, the body is at greater risk for infection and disease.

Many potential stem cells therapies will require immunosuppression, as transplanted stem cells would be seen as "not-self." Another way around this is to use somatic nuclear transfer to create stem cells that the body would recognize as self, and thus people receiving transplants would not need immunosuppression.