Stem Cells

Stem cells are often in the news. These days it’s usually about some advance in research. Sometimes the controversy about using embryonic stem cells resurfaces. Despite all the coverage (pro or con) stem cells are not well understood. What are they and why are they important?

In more ways than one, it’s the potential of stem cells that makes them important. At the moment most of the work with stem cells is still in the laboratory; but that’s changing. Within the next few years stem cells, in one form or another, will be at work in medical applications such as repairing a damaged pancreas or a heart. In fact, stem cells will be used to repair or even re-grow tissues all over the body – skin, liver, lungs, bone marrow. The production of stem cells, their delivery, and procedures for using them will become the basis of an industry. In the not too distant future stem cells, or the knowledge we gain from working with them, will be used in sophisticated repair of the brain and as part of the development of replacement organs. The potential is enormous.

What are stem cells?

Stem cells are found in most multicellular creatures and come in different varieties; all have an important ability: They can fully reproduce themselves almost indefinitely. For example, in mammals like human beings, blood stem cells (hematopoietic stem cells) are active all our lives in the marrow of bones, where they continually produce the many different kinds of blood cells. Therein is another key property for most stem cells; they can become other kinds of cells. The word for this process is differentiate; blood stem cells can differentiate into red blood cells, white blood cells, blood platelets and so forth. The ability to produce different kinds of cells is why stem cells may be used, for example, to repair or replace damaged heart cells – something mature heart cells cannot do on their own.

Stem cell jargon

When you read about stem cells, there are a number of words that jump out – jargon, yes, but still descriptive. Stem cells are classified by their potency, that is, what other kinds of cells they can become, or put another way, their ability to differentiate into other cells. There is a rank order from more to less potent:

Totipotent sometimes also called omnipotent stem cells can construct a complete and viable organism. In short, they are the same as a cell created by the fusion of the egg and a sperm (an embryonic cell). Totipotent cells can become any type of cell.

Pluripotent stem cells are derived from totipotent cells and are nearly as versatile. They can become any type of cell, except embryonic.

Multipotent stem cells can become a wide variety of cells, but only those of a close family, for example blood stem cells (hematopoietic cells) can become any of the blood cells, but not other kinds of cells.

Oligopotent stem cells are limited to becoming specific types of cells, such as endoderm, ectoderm, and mesoderm.

Unipotent stem cells can only produce cells of their own type, for example skin cells. They can renew themselves (replicate indefinitely), which distinguishes them from non-stem cells.

To a certain extent the potency of a stem cell relates to its usefulness. In one view of an ideal (lab) world, only totipotent stem cells would be used because they can become any other kind of cell. The real world (lab or otherwise) doesn’t work that way. For one thing, stem cells of ‘lesser’ versatility than totipotent cells are valuable for use in specific applications. Even unipotent stem cells, lowest on the potency poll, are arguably better suited for some targeted uses than more generic stem cells. Most importantly, for many uses, especially for medical purposes, pluripotent stem cells are extremely versatile – and less controversial.

Avoiding embryonic stem cells

The true totipotent stem cell is a fertilized egg – one embryonic cell. To obtain it means detecting and collecting the cell shortly after fertilization and before it begins to divide. Collecting embryonic stem cells one at a time is very difficult and very expensive. Also, in some parts of the world, using embryonic stem cells is highly controversial, usually on religious grounds. Collecting embryonic stem cells can be considered abortion, since the procedure means the cell(s) will not become an embryo. The label ‘abortion’ is also applied to collecting embryonic stem cells (by gastrulation) shortly after the first fertilized cell begins to divide. These cells, obviously more numerous, are pluripotent and have been the mainstay of stem cell research.

The history of opposition to the use of embryonic stem cells goes back to the 1990’s, when stem cell research was in its own infancy. At that time the only source of viable laboratory stem cells was from in vitro ‘living’ donors. Most of these were ‘harvested’ from fertilization clinics. They were so difficult to acquire that only a few stem cell ‘lines’ (painstakingly cultivated generations of embryonic stem cells) were available. Even those were controversial. The United States banned the taking of embryonic stem cells except for 23 ‘grandfathered’ lines. (This ban was lifted in 2009.)

The controversy over embryonic stem cells can be avoided primarily in two ways. One way is to use adult stem cells. The word ‘adult’ is a bit misleading since the cells may be derived from fetuses, newborns, and children, which is why they’re sometimes called somatic stem cells. It means that these stem cells come from relatively mature tissue, cells that are already differentiated to a certain degree. That’s why adult stem cells are almost always classified as multipotent, oligopotent, or unipotent. The other way is to transform adult stem cells into pluripotent stem cells. Many approaches to this transformation are being explored in labs all over the world. Some approaches are derived from fetal/newborn substances such as amniotic fluid and placental or umbilical tissue. Other approaches use mature (differentiated) stem cells, such as those from skin, and genetically modify them until they become pluripotent. Such cells are called induced pluripotent stem cells, often abbreviated as iPSC.

At the moment, it is not possible to say which approaches to stem cell production and application will be the most effective. Even some that seem unlikely (stem cells from skin cells?) may turn out to be the most economical and useful. Still, this is where the payoff for stem cell research lies – both in terms of scientific knowledge and in profits for medical applications. Consequently the amount of research work in progress is substantial, and often competitive.

Stem Cell Tourism

Because experimental medical techniques and human desperation can add up to big money, there is a developing market for stem cell applications for a variety of medical disorders. Unfortunately, at least for now, with the exception of blood cell transplants and skin cell treatments, most of these applications are either fraudulent or based on shaky experimental results. In general, most stem cell treatments are at best unethical and often illegal; however, their status around the world is a patchwork quilt of laws and regulations (or their absence). It is a near ideal situation for scam artists to lure desperate people into traveling long distances for stem cell treatment that is illegal in their own country. Hence the name: stem cell tourism.

Tracking the Impact of Stem Cell Research

In relative terms, stem cell research is just getting started. Researchers have been at it since the 1950’s; but one of the most important discoveries so far – induced pluripotent stem cells – dates back to only 2006. This means that stem cells are: a. Not yet well understood and b. Their use in medicine is largely experimental and tentative. Here’s a useful listing of what the National Institute of Health (U.S. NIH) considers some of the major open questions about adult stem cells:

• How many kinds of adult stem cells exist, and in which tissues do they exist?
• How do adult stem cells evolve during development and how are they maintained in the adult? Are they “leftover” embryonic stem cells, or do they arise in some other way?
• Why do stem cells remain in an undifferentiated state when all the cells around them have differentiated? What are the characteristics of their “niche” that controls their behavior?
• Do adult stem cells have the capacity to transdifferentiate, and is it possible to control this process to improve its reliability and efficiency?
• If the beneficial effect of adult stem cell transplantation is a trophic effect, what are the mechanisms? Is donor cell-recipient cell contact required, secretion of factors by the donor cell, or both?
• What are the factors that control adult stem cell proliferation and differentiation?
• What are the factors that stimulate stem cells to relocate to sites of injury or damage, and how can this process be enhanced for better healing?
[Source: U.S. National Institute of Health]

SciTechStory Impact Area: Stem Cells

There’s not much debate on the importance of stem cell research. It has already had major impact on our understanding of cell biology, and it will provide more. It is just beginning to have an impact on medicine, with much more to come. In fact, news about stem cell research already occurs once or twice a week (on average) – that pace is likely to increase. As a matter of keeping up, it’s necessary to attempt sorting “lab work” from “practical application,” which is to say sorting promise from delivery. Even at that it will be difficult to select which stem cell stories are ‘significant’.