Sunday, August 14, 2005

Stem Cells, Part 2 – How are they obtained?

Adult Stem Cells

The term “adult stem cells” is somewhat misleading. Adult stem cells do not come exclusively from adults. Human adult stem cells are obtained from a developed person, whether he is a senior citizen, an adult, an adolescent, a child, or even a fetus. Perhaps they should be called “somatic stem cells” because they can be obtained from body tissue. Adult stem cells are cells that have not yet developed into specialized tissue, but are capable of doing so, and are also capable of reproducing themselves indefinitely.

Adult stem cells can be obtained from many places in the body. The most familiar source, because it was the first to be used to treat illness in real persons is from the bone marrow.
Adult stem cells are unspecialized cells that are present in small quantities in already specialized tissue. They are needed by the body because both illness and age destroy tissue cells, and the stem cells can regenerate that damage. Adult stem cells also allow for growth.

Adult stem cells can be used for therapy to treat conditions that involve cell degeneration or even abnormalities. Once again, the flagship example is bone marrow stem cells. A treatment for leukemia, a cancer of the blood, involves taking bone marrow from the patient or a blood relative, extracting the stem cells, treating the extracted material by growing it in a nutritive solution, using drugs or radiation to destroy the patient’s abnormal bone marrow, then reintroducing the extracted material into the patient, where it develops into normally functioning bone marrow. This has been done regularly for more than three decades, and is a well established medical practice.

Researchers have reported finding adult stem cells in bone marrow, muscle tissue, liver tissue, fat, nasal mucus tissue, blood and blood vessels, brain tissue, and skin. Adult stem cells are also richly present in umbilical cord and placenta (“afterbirth”). A thorough summary of the state of research on adult stem cells as of 2003 is located here.

Embryonic Stem Cells

As you will recall from part 1 of this series, what are called embryonic stem cells are really the type of stem cells that are termed “pluripotent”; they are capable of developing into any of the more than 200 types of cells in the human body. This stage of development only exists in nature between conception and a few days later, when the fertilized egg has started to divide, but before the specialization process starts.

There are currently only two ways to obtain embryonic stem cells; the first and most common way is to extract them from a pre-embryo (“blastocyst”), and the other by a process called nuclear transfer, commonly referred to as “therapeutic cloning”.

The only practical source of blastocysts that can be used by scientists is the ones created by them in the laboratory. This process is frequently called “artificial conception” or “in-vitro fertilization”, and is aimed primarily towards assisting women who for one reason or another are unable to conceive in the normal way.

The process involves extracting a large number of eggs from the ovary of a volunteer, combining these ova with the sperm of a volunteer in laboratory conditions, testing the results to determine whether a successful fertilization has occurred, and if so, implanting the fertilized ovum in the uterus of a volunteer. Ideally, the sperm and egg donors are the father and mother, but not always. A woman undergoing this procedure may be unable to ovulate and will need another woman’s ova, or she may ovulate normally but be unable to carry the child, and a surrogate mother will provide the uterus.

This is a very “hit-or-miss” process with a low yield of successfully fertilized eggs. Consequently, because of the difficulty and expense involved, a large number of eggs are extracted and processed in this manner. This leads to a situation where sometimes extra fertilized eggs become available briefly. That is the source of the existing embryonic stem cells that are currently available to the researcher.

The other process, called nuclear transfer, starts with a human ovum also. In the laboratory, the researcher cuts into the ovum, removes the nucleus (the part that carries all the genetic material) and replaces it with the nucleus of an adult cell. If this hybrid cell is nurtured properly, it will develop into a new blastocyst that contains only the genetic information of the person who donated the adult tissue cell from which the nucleus was obtained. Such an individual then will be a clone, with DNA that is identical to the nucleus donor.

In common terminology, this is sometimes called “therapeutic cloning”, but this is also a misnomer. Nothing in the way of therapy can be done with this clone currently (although the research for which it was created may some day do so), so it more precisely should be called “cloning for research”.

A good description of how embryonic stem cells are made can be found here. And this article describes what is involved in Somatic Cell Nuclear Transfer (SCNT).

Next: Stem Cells, Part 3 - How are they handled in research?

Friday, August 12, 2005

Stem Cells, Part 1 - What are they?

One of the most promising areas of medical research is the use of human stem cells. Stem cells are specific undeveloped cells in the human body that can be induced to develop into one or more of the specialized cells of mature human tissue. Stem cells can develop into blood cells, brain cells, kidney cells, or any of the other types of cells that make up our bodies.

This post starts a series of articles that will delve into the science of stem cells; what they are, how they are formed and develop, their present and potential future medical uses, and the controversy surrounding them. Since this is a medical subject, it would be easy for confusing jargon and jaw-breaking terminology to creep in. At the risk of oversimplification in some cases, this article will avoid the Latinate words as much as possible and will use commonly understood terms wherever possible.

To understand stem cells and why they can be so important, it will first be necessary to describe the normal development of a human being from conception to birth.

How a Baby is Formed

Conception occurs as a result of sexual intercourse. The man contributes sperm cells and the woman contributes an ovum, a human egg cell. Both types of cells, sperm and ovum, are incomplete, each having only 23 of the 46 chromosomes required, but they combine into a single complete cell known as a zygote (fertilized ovum). This occurrence is referred to as conception.

At this point, the zygote is a complete entity, capable of developing into a baby, as long as the conditions are right, and as long as a few more key milestones occur as nature designed. The zygote starts to divide inside its outer surface, once every 12 to 20 hours as it passes down the fallopian tube towards the uterus. At any time during the first 14 days, the zygote may separate into two separate zygotes; this is how twins are formed.

By day three, when the zygote consists of a cluster of 16 cells, it has entered a new phase of development that goes beyond simple division. This cluster, which we shall call a pre-embryo, starts to resemble a hollow sphere. By about day five, the pre-embryo has entered the uterus.

It is at this point that the identical cells of the pre-embryo start to differentiate into specialized cells. The outward-facing cells attach to the lining of the uterus and form the placenta, and the inward-facing cells start to form the embryo. By day ten the pre-embryo is firmly attached, and blood circulation begins in the placenta. Medically, this is considered the start of pregnancy.

The process of differentiation leads to the cells in the pre-embryo (textbook name: blastocyst) to organize into three distinct layers, referred to as the germ layers. The term “germ layer” is not related to infection; it comes from the same root as “wheat germ” or “germinate”. Each germ layer is a region of the hollow sphere. Each layer starts to develop specialized cells of specific types. The outer layer will develop into skin cells and brain cells. The middle layer develops into blood cells, muscle cells, and kidney cells. The inner layer becomes lung cells and the cells of various organs. And just to make it confusing, a fourth type of primitive cell is the germ cells, which become sperm in a male or ova in a female.

These four types of cells are referred to as stem cells. The analogy of development is with a plant, where the stem leads to branches, the branches to twigs, and the twigs to leaves, flowers, and all the other glorious plant parts. Stem cells branch into the four types described above, and these in turn develop into more specialized types of cells, eventually leading to more than two hundred different types of cells in the human body.

At about two weeks after conception, the pre-embryo starts to develop a linear pattern of cells known as the primitive streak. It is at this point that it is no longer possible to separate into twins, and it is at this point that the organism is referred to as an embryo. The primitive streak will eventually develop into the central nervous system.

For the next eight weeks the embryo enters a period of rapid development, with the undifferentiated cells forming into organs, limbs, and other bodily structures. At ten weeks, all the recognizable features are present; arms, legs, head and eyes. At this point, it becomes a fetus.

The fetus, which at ten weeks is less than two inches long and weighs less than an ounce, spends the next six months growing in size and complexity inside the mother. At birth, the average child is about 20 inches long and weighs about seven and a half pounds.

The human body, besides being equipped with over two hundred different types of specialized cells, also continues to grow stem cells throughout the body. These stem cells proliferate throughout a lifetime, and eventually develop into one of the two hundred types of cells. This allows the body to grow and to repair damage.

Embryonic and Adult Stem Cells

A stem cell is a cell that can continue to divide and proliferate for an entire lifetime, and develop into specialized cells. Stem cells are categorized in two ways; by their origin, and by their potential to develop a certain way.

All the cells in the pre-embryo are called “pluripotent”; that is, they have the power to develop into any of the germ layer cells, and to further differentiate into more specialized types of cells.

As they start to specialize, they organize into groups by capability. For example, outer layer stem cells can become a number of different types of cells, but they will not become others; that job falls to the middle layer or inner layer types of cells. This restriction leads to the category “multipotent”. As development continues, further specialization occurs, to the point where a stem cell can be considered “unipotent”, that is, only capable of developing into a single type of cell.

A fully developed human, baby to senior citizen, will have throughout his body a collection of different kinds of stem cells, which are usually multi- or unipotent. These cells are referred to as “adult stem cells”. We all have them.

The stem cells in the pre-embryo and embryo are the newest and most potent, capable of differentiating into all types of specialized cells. They can, however, only be obtained by removing them from embryos. Consequently, these are referred to as “embryonic stem cells”.

Next: Stem Cells, Part 2 - How are they obtained?

Wednesday, August 10, 2005

Names That Fit

I have always been amused by the game of inventing names for people that define the person's occupation. At the end of each program of "Car Talk" on PBS radio, Tom and Ray Magliozzi read a long list of credits for made-up staff members. I have prepared my own list. Feel free to comment with your own creations.



MasseuseOphelia Thye
Yoga instructorBen Dover
ProctologistSeymour Butz
CounterfeiterBill Passer
Carnival operatorFerris Wheale
Human resources managerBennie Fitz
PilotAlana R. Plaine
UrologistI. P. Daly
Mountain climberCraig Mounter
Soft drink manufacturerAaron D. Waters
ExplorerBen Dare
GynecologistPat McGroyne
Burlesque dancerFannie Mae Jiggle
High-stakes gamblerBetsy Normis
Holdup artistRobin Banks
PoliticianJerry Mander
OptometristI. Kinsey Clearly
AccountantCarrie D. Balance
Diner waitressAnita Koffey-Black
Traffic copTerry Knott
TailorKen Eumenides
Macrame artistMatt Weaver
Football cheerleaderVictor E. Dantz
Sporting goods salesmanDennis Racket
Justice of the peaceMary N. Haste
Retired senior citizenRandy O'Gote
Fast food workerU. Wanda Burger
Project managerRoy L. Payne-Diaz