Heart disease and stem cells

 
 

What are stem cells? -^-
Stem cells are very special body cells. Serving as a sort of repair system, they have the potential to develop into many different cell types in the body. Theoretically they can divide without limits to renew themselves, or divide and differentiate into other, specialised cells such as a muscle cell, a red blood cell or a brain cell. Stem cells have the ability to form different types of tissues and organs, and they are present in every adult as well as in embryos. Stem cells divide to form:
- one daughter that goes on to differentiate (it specialises in a task);
- one daughter that retains its stem-cell properties.


Are there different types of stem cells? -^-
Several terms are used to describe the developmental potential of stem cells:

1. Totipotent cells. In mammals, totipotent cells have the potential to become:

- any type in the adult body;
- any cell of the extraembryonic membranes (e.g., placenta).

The only totipotent cells are the fertilised egg and the first 4 or so cells produced by its cleavage (as shown by the ability of mammals to produce identical twins, triplets, etc.).

2. Pluripotent stem cells. These are true stem cells, with the potential to make any differentiated cell in the body, but cannot contribute to making the extraembryonic membranes (and thus cannot replace a fertilised egg cell).

Three types of pluripotent stem cells have been found:

- Embryonic stem cells. These can be isolated from the inner cell mass of the blastocyst - the stage of embryonic development when implantation occurs. For humans, excess embryos produced during in vitro fertilization procedures are used. Harvesting cells from human blastocysts is controversial because it destroys the embryo, which could have been implanted to produce another baby (but often was simply going to be discarded);
- Embryonic germ cells. These can be isolated from the precursor to the gonads in aborted fetuses;
- Embryonic carcinoma cells. These can be isolated from teratocarcinomas, a tumor that occasionally occurs in a gonad of a fetus. Unlike the other two, they are usually aneuploid.

All three of these types of pluripotent stem cells can only be isolated from embryonic or fetal tissue and can be grown in culture, but only with special methods to prevent them from differentiating.

3. Multipotent stem cells (sometimes termed 'adult stem cells'). These are true stem cells but can only differentiate into a limited number of types. For example, the bone marrow contains multipotent stem cells that give rise to all the cells of the blood but not to other types of cells.
Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that - when one accumulates sufficient mutations - produce a clone of cancer cells.


What can stem cells be used for? -^-
It is the dream to use stem cells for human therapy, since many medical problems arise from damage to differentiated cells.Examples are:
- Insulin-dependent diabetes mellitus (IDDM) where the beta cells of the pancreas have been destroyed by an autoimmune attack;
- Parkinson's disease; where dopamine-secreting cells of the brain have been destroyed;
- spinal cord injuries leading to paralysis of the skeletal muscles;
- ischemic stroke where a blood clot in the brain has caused neurons to die from oxygen starvation;
- multiple sclerosis with its loss of myelin sheaths around axons;
- blindness caused by damage to the cornea.

The great developmental potential of stem cells has created intense research into enlisting them to aid in replacing the lost cells of such disorders. While some success has been achieved with laboratory animals, not much has yet been achieved with humans. There are exceptions: the differentiated progeny of cultured human epithelial stem cells can be used to replace a damaged cornea. This works best when the stem cells are from the patient (e.g. from the other eye). Corneal cells from another person (an allograft) are always at risk of rejection by the recipient's immune system. Another example that is shown in the film 'Beat of the Heart', where patient's bone marrow stem cells are used to induce growth of blod vessels in damaged heart tissue.


What are the current problems involving stem cell usage? -^-

1. Imprinted Genes.
Sperm and eggs each contain certain genes that carry an "imprint" identifying them later in the fertilized egg as being derived from the father or mother respectively. Creating an egg with a nucleus taken from an adult cell may not allow a proper pattern of imprinting to be established. When the diploid adult nucleus is inserted into the enucleated egg (at least those of sheep and mice), the new nucleus becomes "reprogrammed". What reprogramming actually means still must be learned, but perhaps it involves the proper methylation and demethylation of imprinted genes. For example, the inactive X chromosome in adult female cells must be reactivated in the egg, and this actually seems to happen.

2. Aneuploidy.
In primates (in contrast to sheep, cattle, and mice), the process of removing the resident nucleus causes molecules associated with the centrosome to be lost as well. Although injecting a donor nucleus allows mitosis to begin, spindle formation may be disrupted, and the resulting cells fail to get the correct complement of chromosomes (aneuploidy).

3. Somatic Mutations.
This procedure also raises the spectre of amplifying the effect(s) of somatic mutations. In other words, mutations that might be well-tolerated in a single somatic cell of the adult (used to provide the nucleus) might well turn out to be quite harmful when they become replicated in a clone of cells injected later into the patient.

4. Political Controversy.
A universal stem cell treatment (which is often called "therapeutic cloning" even though no new individual is produced) uses a cultured blastocyst that can serve as a source of embryonic stem cells. But that same blastocyst could theoretically be implanted in a human uterus and develop into a baby that was genetically identical to the donor of the nucleus. In this way, a human would be cloned. And in fact, Dolly and other animals are now routinely cloned this way. It is seen as unethical to produce, culture and use such stem cells for therapeutic purposes, since the cells are a theoretical form of human life.

For many medical problems there is no possibility to isolate stem cells from the diseased patient and cells from a donor (fetal cells) must be used. If embryonic cells are not allowed to be used for human stem cell therapy then adult donor cells could be used. These, however, face the threat of rejection by the immune system of the patient. One way to avoid the problem of rejection is to use stem cells that are genetically identical to the host. Somatic-cell nuclear transfer may be a solution to this problem that is subject of current research. In this technique the use of fetal cells would not be necessary:

- A human egg has its own nucleus removed and is replaced by a nucleus taken from a somatic (e.g., skin) cell of the patient. The now-diploid egg is allowed to develop in culture to the blastocyst stage when embryonic stem cells can be harvested and grown up in culture. When they have acquired the desired properties, they can be implanted in the patient with no fear of rejection.

The spectre of the procedures are so abhorrent to many that they would like to see such therapies banned despite their promise for helping humans. In fact, many are so strongly opposed to using human blastocysts - even when produced by nuclear transfer - that they would like to limit stem cell research to adult stem cells (even though these are only multipotent).

Two possible solutions have so far been demonstrated only in mice:

- Embryonic stem cells can be derived from a single cell removed from an 8-cell morula. We know that, in humans, removing a single cell from the morula does not destroy it: the remaing cells can develop into a blastocyst, implant, and develop into a healthy baby.

- In altered nuclear transfer (a modified version of somatic-cell nuclear transfer) a gene necessary for later implantation is turned off (by RNA interference) in the donor nucleus before the nucleus is inserted into the egg. The blastocyst that develops i) has a defective trophoblast that cannot implant in a uterus; ii) but the cells of the inner cell mass are still capable of developing into cultures of embryonic stem cells. (The gene encoding the interfering RNA can then be removed using a special technique.) If these procedures work in humans, neither would involve the destruction of a potential human life.

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