STEM CELLS INFORMATION Q&A

What’s left to learn about stem cells?
We know that stem cells are present at all stages of our life. Stem cells found in early embryos have the potential to become different types of cell, while adult stem cells are more specific. The questions we are trying to answer are: can we identify all stem cells? Can we grow them in large numbers in the lab? Can we make them give rise to any cells we wish? Can we use stem cells to treat cancer, ageing and degenerative diseases?

Does every multicellular organism have stem cells?
Yes. In mammals, there are two main types of stem cells: embryonic, which are generated from early embryos, and adult, which are found in various tissues and contribute to the repair and replenishment of our tissues.

For a long time it was thought that once the stem cells changed to form the various cells that make up our organs, it was impossible to make them revert back to the initial stem cell state.

However, the Nobel prize winner Shinya Yamanaka reported in 2006 that adult cells can be turned back to the embryonic stage by simple genetic manipulation.

Who first discovered stem cells?
The concept of stem cells was fi rst mentioned by Valentin Haecker and Theodor Boveri in the 19th century. In parallel, Artur Pappenheim, Alexander Maksimov, Ernst Neumann and others used it to describe a proposed origin of the blood system.

As the field progressed, the term ‘stem cell’ has been used to describe the capacity of stem cells for self-renewal as well as the ability to give rise to all cell types that make up our bodies.

Do stem cells have to be prompted in some way to repair the body?
Adult stem cells need prompting if a quick repair is needed, and we can achieve this in the lab. Stem cell prompting in the body is a bit more tricky, but can occur in response to specific stress or injuries.

STEM CELLS IN ALZHEIMER'S RESEARCH BASIC INFORMATION

Because the mouse models of Alzheimer’s don’t truly duplicate the disease, researchers have tried making the genetic changes that cause early-onset Alzheimer’s in a variety of cells grown in the lab. This technique has been helpful in letting scientists understand how these genes work normally and what happens when they carry the mutations that cause Alzheimer’s.

However, until recently, scientists weren’t able to make and study these genetic changes in human neurons because, before the advent of human embryonic stem cells and technologies for reprogramming other cells, making human neurons in the lab was, for all practical purposes, impossible.

Scientists can use human stem cells — either embryonic stem cells or induced pluripotent stem cells from tissues — or neuronal stem cells from fetal tissue to grow human neurons that have the genetic mutations that lead to Alzheimer’s. Then they can study what’s different about those neurons and perhaps come up with drugs that repair the damage or keep the damage from spreading.

Similarly, scientists can take other types of cells — say, from the skin — from people with sporadic Alzheimer’s, reprogram them to become pluripotent stem cells, and grow neurons from them. (Larry’s lab at the University of California–San Diego is using this technique.) Then they can compare the behavior of human neurons with the genetic architecture of hereditary Alzheimer’s, sporadic Alzheimer’s, and normal neurons to see where the similarities and differences lie.

This comparison may help researchers determine why some people are less susceptible to Alzheimer’s than others, as well as identify the triggers and mechanisms of the disease — which may, in turn, lead to new therapies for treating Alzheimer’s. (Scientists are using similar approaches to study other diseases, too, such as Lou Gehrig’s and Parkinson’s.)

Scientists also are trying to find ways to use the brain’s own stem cells to replace damaged cells in Alzheimer’s and other diseases. Of course, growing neurons isn’t the only thing you can do with stem cells.

You can also

✓ Use them in cell transplant experiments. Several labs are experimenting with transplanting healthy cells into animals to see whether they replace or rescue damaged or defective cells in mouse models of Alzheimer’s.

✓ Use them to deliver material to specific regions of the brain. In Alzheimer’s patients, their brains may have enough of certain material, such as growth factors, but the material doesn’t get to the regions of the brain that need it. Scientists are exploring ways of using stem cells and other methods to deliver these potentially important materials to the appropriate parts of the brain.

✓ Use them to develop potential drug therapies. Scientists can test drug therapies on cells with hereditary or sporadic Alzheimer’s to see whether the therapies make the cells behave more normally.

Unfortunately, the idea of manipulating the brain’s own stem cells to solve problems outside their normal purview is easy to draw on a blackboard, but not so easy to put into practice. But it’s an exciting possibility with implications for all kinds of neurodegenerative diseases, so the scientific community is eagerly pursuing it.

For decades, researchers thought brains in humans and other mammals were devoid of stem cells. But the human brain (and animal brains, for that matter) does contain two small populations of stem cells. One cache supports the olfactory system (the tissues and organs involved in sensing smell), and the other is in a
region of the brain that’s involved in processing information and forming new memories.

Many researchers are trying to figure out whether these indigenous brain stem cells can be induced to provide rescue activity to regions that are damaged in Alzheimer’s and other neurodegenerative diseases. For example, perhaps these stem cells could be programmed to spawn new neurons to replace damaged or dead ones.

POSSIBILITIES AND LIMITATIONS OF EMBRYONIC STEM CELLS

Embryonic stem cells hold a great deal of promise in treating or even curing a range of devastating diseases. But potential isn’t reality, and, even with all their promise, embryonic stem cells can’t do some things — at least, we don’t think they can.

Unfortunately, these nuances are often missed or blurred when a promising idea or test captures headlines. So here’s a summary of what we really know about embryonic cells: what they can do, what they can’t do, and what we think they may be able to do — not today, but in the relatively near future.

What embryonic stem cells can do?
To figure out how cells develop normally and what goes wrong when they don’t, you need a lot of cells to observe and test. Perhaps the most useful property of embryonic stem cells, at least for today’s researchers is that when you grow them properly, you can make lots and lots and lots of embryonic stem cells.

And you can, in turn, use those embryonic stem cells to make lots of specific types of cells. If you want to figure out why pancreatic beta cells misbehave in some types of diabetes, for example, and then find ways to repair or replace them, you need a lot of pancreatic beta cells.

Several research groups have already started testing drugs using cells derived from embryonic stem cells, and a number of researchers are well on their way to transplanting such derivative cells into animals to test the cells’ capacity to change a disease — reduce symptoms or reverse damage. (Scientists need to do these types of tests on animals, and the results have to meet certain benchmarks before they can conduct similar tests on humans.)

Embryonic stem cells seem to be able to make all types of cells in the adult body, which makes them particularly useful in investigating the causes of and possible treatments for a wide range of diseases, from central nervous system disorders like ALS to chronic conditions like diabetes and heart disease.


What embryonic stem cells can’t do?
Even with all their wondrous abilities, embryonic stem cells have their limitations.

For example, they can’t make a baby. That’s because embryonic stem cells are derived from the inner cell mass of a blastocyst. Those inner cells can’t make the placenta that provides nourishment for a developing baby, or the umbilical cord that delivers nutrients to the fetus. Embryonic stem cells can’t be used to clone an adult (at least, as far as we know today).

And they can’t cure disease in and of themselves. You can’t just inject a syringe-full of embryonic stem cells into a mouse or a human and expect them to identify and correct a problem. You have to know what kind of cells to make from embryonic stem cells, how to purify them, and where to put them in the body.

Plus, in order to make testing any potential treatments safe (and to give those potential treatments a strong likelihood of being effective), you need a lot of reliable information about both the cells and the potential
treatment.

Perhaps most important, embryonic stem cells can’t solve all our medical problems and issues overnight. Even with all the exciting things we can do with them now, it’s going to take time — quite a lot of it — to fulfill many of the promises these fascinating cells seem to hold.

What embryonic stem cells may be able to do?
With good ideas and rigorous research, scientists see virtually no limit to what we may be able to do with embryonic stem cells a generation or two from now. The ideas are the key: Creative ideas lead to realities that nobody ever imagined. (After all, do you think the guys who invented the first computer foresaw the Internet?)

Some of the things scientists are daring to imagine now:

✓ Creating cells and tissues that can be transplanted into humans
✓ Developing drugs that are cheaper to make and more effective in treating disease

✓ Testing toxins and environmental factors to see how they affect human development and health
✓ Growing “replacement parts” — new limbs, organs, and tissues that the body accepts as its own, without suppressing the immune system or running the risk of infection

We’re years away from realizing many of these dreams, of course. Human embryonic stem cell research is only about 10 years old; work with adult stem cells, on the other hand, is more than 40 years old, which is why we know so much about some kinds of adult stem cells and have been able to develop some practical applications for them.

EMBRYONIC STEM CELLS PROPERTIES BASIC INFORMATION

In the movie “Star Trek IV: The Voyage Home,” the crew of the Enterprise travels back in time to 20th-century Earth, and Dr. McCoy helps a woman undergoing dialysis. As she’s being wheeled down a hospital corridor, she joyfully tells everyone, “Doctor gave me a pill, and I grew a new kidney!”

Okay, that kind of biological miracle is still the stuff of science fiction. But embryonic stem cells hold enormous potential for giant leaps in medical treatments because of their unique properties:

✓ They can divide and grow more or less indefinitely.
✓ They can develop into any cell type found in the adult body.
✓ They have an incredibly lengthy shelf life, so they can be stored for very long periods without losing their potency.

Growing and growing and growing . . .
Left to their own devices, cells in the blastocyst eventually differentiate, or begin developing special characteristics of job-specific cells. Some become neurons, for example — the brain cells that control thought and movement.

Others spin off into red or white blood cells, or heart muscle cells, or liver cells, and so on. DNA, which provides the blueprints for cell development, and RNA, the user’s manual stating which part of the blueprint to follow, determine which job each cell takes on.

In the lab, though, scientists can delay the reading and implementation of the genetic instructions that tell cells to specialize by isolating the inner cells from blastocysts, transferring them to Petri dishes, and feeding them a mixture of appropriate nutrients (called a growth medium or culture medium) so they can
continue to grow.

Under the correct conditions, embryonic stem cells read the genetic instructions for self-renewal and continue to grow until they’re exposed to signals that tell them to read the genetic instructions for specialization.


Cells like to touch other cells, so scientists usually line the Petri dish with alayer of other cells — most commonly embryonic skin cells from mice that have been treated so they won’t grow. The cells in this layer are called feeder cells.

The inner cells from a blastocyst are placed on top of the feeder cells, and a growth medium (a broth rich in the nutrients the cells need to thrive) is added. Depending on what’s in the growth medium, these inner cells can continue dividing into more embryonic stem cells, or they can begin differentiating into specific categories or types of cells.

One of the risks associated with using mouse feeder cells to grow human embryonic stem cells is that the human cells may be infected with viruses or contaminated with other unwanted material from the mouse cells. Researchers have come up with other ways to grow embryonic stem cells, but only time will tell us whether these alternative methods are as useful and reliable as using mouse cells.

Assuming the relocation of the blastocyst’s inner cell mass into a Petri dish is successful — and that’s not always the case — the embryonic stem cells grow until they crowd the dish. Then they’re removed from the original dish, divided up, and placed into several new dishes with fresh growth media.

This process is called subculturing, and each round of subculturing is called a passage. Scientists can separate, freeze, and store batches of cells at any stage of the subculturing process. They also can ship them to other researchers after they’ve verified that the cells are stable and usable.

It takes at least six months and several passages to create an embryonic stem cell line — that is, millions of cells derived from the original inner cell mass of the blastocyst that meet two critical conditions:

✓ They retain their ability to grow into any kind of cell in the adult body.
✓ They appear to have no genetic defects.

Scientists use a method called karyotyping to make sure that stem cells have the correct number of chromosomes. Normal human cells have a total of 46 chromosomes, paired in sets of two; you inherit one of each set, or 23 chromosomes, from each parent.

Embryonic stem cells’ ability to grow and divide practically indefinitely under the right conditions is an important property for medical research and developing useful treatments. It takes millions of cells to conduct reliable experiments, and one of the biggest eventual challenges in in using stem cells to treat illness is creating enough of them to do the job.

TOP UNANSWERED QUESTIONS TO EXPLORE ABOUT STEM CELLS

Scientists have been studying adult stem cells for more than 40 years and embryonic stem cells for more than 20 years. They’ve uncovered a lot about both kinds of stem cells, but there’s a lot they still don’t know.


Questions researchers are still seeking answers to include the following:

✓ How many kinds of adult stem cells are there?

✓ Where do adult stem cells live in specific tissues?

✓ What control mechanisms do stem cells use to maintain their selfrenewal capabilities?

✓ What genetic mechanisms control stem cells’ ability to make one or more kinds of differentiated cells?

✓ Why don’t adult stem cells differentiate automatically when they’re surrounded by differentiated cells?

✓ Why can embryonic stem cells grow and make more of themselves in the lab for a year or more, while most adult stem cells have far more limited self-renewing capabilities in a Petri dish?

✓ How do stem cells know when to make more of themselves and when to make cells for specific tissues?

✓ Why don’t all stem cells “home in” to their proper location the way blood-forming stem cells do when they’re transplanted into a living body

✓ If you introduce stem cells into specific tissues in a living body, do they stay where you put them, or do they wander aimlessly around the body’s tissues?

✓ How long do transplanted stem cells stay in the body?

✓ If you reprogram adult cells to behave like embryonic stem cells, are the reprogrammed cells completely normal, or does the reprogramming process mess with the genetic instructions?

✓ In their normal environments (known as niches), can adult stem cells really make differentiated cells for tissues other than their tissue of origin?

✓ Is there a master adult stem cell — one that, like embryonic stem cells, can make any type of cell in the body?

Modern stem cell science is pretty young, so it’s not surprising that researchers still don’t know the answers to some relatively basic questions. As Lao Tzu, the father of Taoism, is credited with saying, “The wise man knows he doesn’t know.”