Posts Tagged ‘stem cells’

Your Oldest Treasure

Sunday, July 18th, 2010
And you thought this was old...

And you thought this was old...

What do you own that is 600 million years old? Your old suit? That little league baseball glove? Your cologne? In fact, every man possesses something that old, and believe it or not, it’s a gene. Not the clothing kind, but the kind you keep in your genome, in your chromosomes. We’ve talked about the Y chromosome in this space but lets take a moment to focus on a single tiny gene.

Tucked away in every cell of your body is a gene called Boule, a piece of DNA critical for sperm production. A colleague of mine just announced that the Boule gene is present in every organism from insects like fruit flies, to sea urchins, roosters, fish and man. It is in invertebrates and vertebrates alike. That is, this tiny bit of DNA has remained essential for making sperm through 600 million years of evolution. Surely the oldest treasure you own.

But what’s really impressive about the Boule gene is that is has not changed over time. And change is the rule with every other known gene involved with reproduction in every species. In fact, evolution of reproductive traits is how a species diverges from other species. It gives each species its identity. And this change can be very rapid: in some fish, reproductive traits are observed to change in fewer than a dozen generations. So why would this one gene stay the same?

We think that the Boule gene has remained true over 600 million years because it is essential for reproduction. Boule is a “quality control” gene that ensures all goes well as sperm are made. Just as you would want your new car to be well inspected so it is safe to drive when you buy it, you want your sperm to be reproductively fit. In fact, if the Boule gene is removed, sperm production stops entirely. Not a single sperm is made in its absence. Now that’s control.

What’s also impressive about the Boule gene is that since it is linked to sperm production, it means that sperm are very, very ancient cells. Seems that nature sticks with what is tried and true and feels no need to experiment with magic potions or fairy dust to get the job done. Reminds me of what Einstein once said while reflecting on relativity and physics: “God does not play dice.” When it comes to reproduction, the Boule gene phenomenon suggests that he may take even fewer chances.

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Posted in male infertility, men's health, sexual health | 1 Comment »

Stem Cells are People Too

Sunday, March 14th, 2010
A stem cell in a dish is worth a hundred different therapies.

A stem cell in a dish is worth a hundred different therapies.

Not all stem cells are alike. News to you? Maybe not, but it has hit researchers pretty hard over the past several weeks. As you may have garnered from prior essays on this blog, stem cells are potentially capable of morphing into many different tissues, such nerves, heart or liver, and are the next wave in medical therapy for all kinds of diseases affecting both the young and the old. The medical treatment that they will bring to the table is called “personalized, cell based therapy.”

One huge problem is that the best kind of stem cell, the one that can do the most, is created from embryos. The embryonic stem cell has many “issues” though: derived from embryos, retrieval ethics, not patient specific, created by cloning, inefficient to produce and the like. Because of this, research has focused on alternatives like transformed adult stem cells or our very own untransformed testicular stem cells. The news today concerns the quality of adult-type stem cells that are “reprogrammed” and transformed into embryonic-like stem cells, also termed induced pluripotency stem (iPS) cells.

Well, there appear to be growing pains for the iPS cell, an embryonic stem cell alternative. Developed in 2006 from adult skin cells, researchers genetically manipulated a specialized adult cell, transforming it back to an unspecialized state. Since then, hundreds of labs have leaped into the burgeoning adult stem cell field.

The ideal stem cell is like a blank slate. It is capable of becoming any other tissue, and is immortal. True embryonic stem cells are like this, but, according to several recent publications, many iPS cell lines are not really blank slates. Also, it appears that nerve and blood cells made from iPS cells grow poorly and age quickly and may even “remember” what cell from whence they came. Some even conclude that iPS cells may not even be considered a practical choice for cell-based therapy down the line.

The realization that iPS cells are not exactly like the gold standard embryonic stem cells has slowed the field down a bit, but it is an important observation. Like people or even wine, stem cells are a bit different from one another, each with their own personality, temperament and potential. Some do this better than that, and others do that better than this. It suggests that stem cell-based therapy may eventually involve tapping into a mixture of different stem cells to cure the problem. Now that’s an old fashioned idea: a little of this and a little of that…

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Keeping the Family Jewels Shining

Saturday, January 2nd, 2010
Heirlooms for the species.

Heirlooms for the species.

As a living, breathing being on this good earth, we tend to take things for granted. The ability to have offspring can be one of them. That is, until the day that a serious medical condition like cancer rears it ugly head and puts childbearing at risk. In addition to the sterilizing effect of cancer treatments, the mad rush to treat the disease often marginalizes efforts to preserve fertility. Fire all the canons and check for collateral damage later.

Fertility preservation seeks to protect men, adolescents and children from a common, serious and impactful side effect of cancer treatment: infertility. The goal of fertility restoration is to empower patients who are cured and potentially infertile to bear children. These related fields have burgeoned recently because medical care is now shifting from curing cancer to improving the quality of life among survivors. And without a doubt, for many, fertility is a key quality of life issue at some point. Thankfully, exciting new methods of restoring fertility have already been developed and even newer technologies are under study.

Classic techniques for fertility preservation in men include gonadal shielding and sperm banking. Gonadal shielding uses lead-based devices to protect the testicles from being struck directly by sterilizing radiation treatment. Sperm banking is the process of freezing healthy sperm before cancer treatment begins for later use to conceive. But there is more. For patients who are too young to bank sperm, for those who have precious little time to bank sperm, or for those who have no ejaculated sperm to bank, testis sperm retrieval by biopsy (TESE) or needle aspiration (TESA) for banking is now possible before cancer treatment. In fact, in some cases of testis cancer, it is possible to remove only the cancerous nodule instead of the whole testis, or to freeze sperm from the testicle after it is surgically removed. These are now routine ways to preserve fertility in men.

Fertility restoration for men has also seen real advances lately. Sperm “mapping” is an innovation that I developed for men who survive cancer treatment but have no sperm in the ejaculate. It non-invasively and non-surgically deciphers whether there are small numbers of mature sperm in the testis, too few to get into the ejaculate, but usable nonetheless. In men who sustain nerve injury from cancer surgery and who are unable to ejaculate, a special medical instrument can produce an ejaculate for fertility purposes in a process termed electroejaculation. Techniques such as these are valuable tools to help men deemed “sterile” after cancer treatment to become fathers.

One of the most exciting areas of fertility restoration involves stem cell technology. Yes, the “promise” that we have all heard about stem cells curing disease will likely find its way into the fertility field as well. In pre-pubertal boys with cancer, ejaculated sperm is not present. Despite this, it may be possible to freeze the early stem cells from the testicles of boys before sterilizing treatment. After thawing, these “adult” stem cells may later be used to create sperm after further growth in a Petri dish or after transplantation back into the same individual. Also on the horizon is our ability to take skin cells from a sterile man, convert them into an embryonic-like stem cells and then “drive” these cells to become mature sperm in a dish–a true “artificial testicle.” So, with the belief that hope can cure misery, the world of science has taken fertility research from science fiction to reality. Not convinced? Stay tuned!

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Posted in male infertility, men's health, testis cancer | 4 Comments »

No Men. Just Sperm.

Thursday, July 9th, 2009

Does this look like a real sperm? Do you believe in UFO's?

Does this look like a real sperm? Do you believe in UFO's?

We saw it coming. We created stem cells from testis tissue and published it earlier this year and I mentioned previously that it should be possible to do the opposite and create sperm from stem cells. Well, as announced yesterday from a research group in Britain, that possibility is closer to becoming a reality. Sperm created in a Petri dish. Artificial sperm.

Published yesterday in the journal Stem Cells and Development, this is being hailed by the press as “breakthrough” research. Now call me cautious, or call me a stem cell biologist, but I get suspicious when that term is used to describe medical research. More on that later. The technique, discovered by a team of biologists at the University of Newcastle in England and led by Dr. Karim Nayernia, purports to have created actual moving sperm from human embryonic stem cells. Not in a testicle, but in a laboratory dish. This group has some amount of “street cred” as they had previously published a paper in which mouse embryonic stem cells were used to produce in a dish. In fact, these sperm were injected into mouse eggs, formed mouse embryos and baby mice. However, a close look at the small print reveals the mouse pups all had “growth abnormalities” and died after birth.

Now back to being Mr. Cautious. If you look closely at the figures and video in the human paper, you might not be convinced that these are actual sperm. Pictures are a little too fuzzy. Kind of UFO-like. Could they really be neurons instead of sperm? Also, the sperm neither look nor move quite like what we would expect with normal sperm. Finally, some of the “reporter” genes that are used to classify the genetic origin of the cells are not working all that perfectly. Why didn’t the researchers provide more convincing evidence of the universally recognized elements of a sperm including the acrosome, midpiece with mitochondria and characteristic axonemal structure? Oh, and where are the controls?

There is no doubt that Dr Nayernia will face scrutiny for this work, as he has before. And this is all good. Because if the scientific world believes that it is true, then this is an amazing feat of science with enormous potential. For such acceptance to occur, a confirmatory study by another group will likely be necessary. Maybe ours, as we are investigating the same concept but in a radically different and much more feasible way—by trying to create an entire artificial testicle instead.

There are other meaty issues surrounding this research. Is it safe? Is it practical? Remember how inefficient it was to clone Dolly the lamb? Inefficiency runs rampant in any reproductive process. As an example, say that you discovered that humans can reproduce through sex and tried to license the process. With a 20% efficiency rate, you would probably be denied the license. On the other hand, if it is really true, this work has demonstrated the enormous potential of embryonic stem cells, as making a sperm is about as complex a process of cellular transformation that you will find in the body. Making bone, cartilage or heart cells should be much easier. Will it ever get to the point in which a healthy child might be conceived in this way? If that happens, then I might start thinking more about the real role of man in mankind. But not sooner. After all, if men become redundant in the reproductive process, who will replace men’s uncanny knack for opening jars?

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Posted in male infertility | 24 Comments »

How Are Stem Cells Like Wine Grapes?

Wednesday, May 27th, 2009

Stem cells, like wine grapes, need tender nuturing to reach their potential.

Stem cells, like wine grapes, need tender nuturing to reach their potential.

Silicon Valley started in a small garage across the way from Stanford University by one man named Hewlett and another named Packard. There’s an historic plaque on that garage now, and a worldwide industry surrounds it. Stem cell research has just as much potential.

Last week, I mentioned that I was a believer, that I have seen things happen in stem cell research that others haven’t. Collaborating with Renee Reijo Pera, PhD at Stanford, we have been developing adult stem cells that would not involve embryos, or viruses, and that would not be rejected from the body. It all started when we put our heads together and thought hard about how sperm are made and how stem cells are grown. From this line of thinking, we concluded that the adult human testicle would be a great place to create a stem cell. Why? Because the first thing a developing embryo does as it begins to grow is to set aside cells and designate them as “germ” or reproductive cells. Much later on in fetal life, other tissues develop. So, germ cells are special and very closely related to embryonic stem cells; that is, they are very “stem like.”

The next problem, and a big one at that, was how to take adult stem cells and “reprogram” them to become embryonic-like stem cells. This took the better part of four years to figure out. And, like your grandmother’s great apple pie, the secret is in the recipe. Indeed, we found that just the right combination of feeder layers (a layer of cells in a petri dish which help the stem cells to develop) and bathing solutions were instrumental in nurturing these rare testis stem cells to become embryonic-like in a laboratory dish. I developed a lot of respect and a certain fondness for these rare and special cells through this process of discovery. The care lavished on them reminds me of winemakers and their finicky pinot noir vines, which require the right conditions and care to produce their transcendent fruit. Both require a delicate touch.

So, slowly, with persistence, we were able to generate a very “stem like” adult germ cell in a dish starting from a testicle. We showed that, like a real embryonic stem cell, this cell could begin to form the different layers of the body, including nerve, in a dish. What is still not clear from all of this work is exactly what kinds of body tissues can be made from this cell. Can we make an entire heart? How about a clavicle? Or can we just make sperm? This is what the next four years of research are for. In any case, this discovery may help to bypass the whole moral debate surrounding embryonic stem cells. There would also be no viruses to worry about, nor tissue rejection issues to dodge, because your body would simply be rebuilding itself.

Understand that this research is still in its infancy, but it’s a whole new world of medicine, where whole organs may be regrown, and sight and fertility restored. With more time, this kind of research may be as earthshaking as the discovery of antibiotics a century ago. Stem cell research is likely to be even more transformative than this. May the wonder and awe from scientific discovery never end.

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Stem Cells, Snake Oil and You

Monday, May 18th, 2009

Stem cells are past the snake oil stage of medical treatment

Stem cells are past the snake oil stage of medical treatment

We’re way past bottled snake venom now. The new miracle medical cure lies deep within us, in our stem cells, if we can only figure out how to tap into them. 100 days into President Obama’s term, and it seems that the scientific community here in the U.S. might just be getting the fuel it needs to make major headway. The ban on using federal research money for stem cell research has partially been lifted, and I imagine that more funding is to come. A wise investment, I say. The potential for stem cells in medical care is simply enormous. I say this without hint of idealism, or romance, since I myself have seen what stem cells can do in my research with Stanford.

True stem cells are “pluripotent.” That is, they have the ability to become all of the different types of cells in the body. They could be used to rebuild or replace damaged tissue that is difficult or impossible for our own bodies to repair. Take nerves for example. If nerve cells degenerate, as occurs say with multiple sclerosis, one could apply stem cells to replace those degenerated nerve cells. These same stem cells could also replace damaged tissue associated with lung cancer, or Parkinson’s disease, or diabetes. Many conditions, including these, can currently be medically controlled, and made easier to live with, but they can’t be cured. Stem cells may change all that. For example, if eyesight has been lost due to corneal damage, we may be able to use stem cells to grow a new cornea, and restore lost vision.

There are many hurdles to overcome, some of them highly technical problems dealing with how to get from point A to point B. And cells that come from someone else can potentially be rejected. Even still, there are questions that may never be satisfactorily answered, ethical and cultural questions. Truly pluripotent stem cells are currently taken from embryos. When embryos get older, we call them fetuses, and when they are born, we call them children. The meaning of taking basically the seedling of a human being to treat another isn’t easy for some people to swallow. For others, the idea of cell-based therapy goes against deeply rooted notions of what is natural on this good earth. How you feel about this reaches into the most sacrosanct places in the heart and mind.

But there are other possibilities besides taking stem cells from embryos. “Adult” stem cells are stem cells made not from embryos, but from the tissues of fully grown adults. Bone marrow is a good example. Within bone marrow, special cells exist that can create all the cells within your blood. It could be that almost every tissue in the adult body has some kind of adult stem cell within it. Such cells might be able to be harvested from the same patient who needs treatment. Manipulated in a dish, they could be coaxed into other tissues, just like embryonic stem cells. This would avoid the issue of rejection discussed earlier, as well as the ethical questions raised from using embryonic stem cells. Currently, this coaxing is only possible with the help of viruses that introduce specific pluripotency genes into the adult cells and transform them into embryonic like cells. But who knows what tomorrow will bring? As I said, I have seen the potential already in a petri dish. More on that in my next posting.

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