Turek On Men's Health » stem cells

It’s in the Steak

Paul Turek, MD — Tue, 21 Feb 2012 16:00:48 +0000

Hope is a core value of children (Drawing courtesy Sophia Turek, age 7)

In quiet moment on the couch, I recently asked my 8-year old daughter what the word “hope” means to her. “If life were a meal, hope belongs in the steak,” she said.

The food metaphor didn’t surprise me, as with most kids her age, she thinks about it a lot. What did interest me was that, in her view, hope takes center stage. It’s not the cupcake for dessert. Or a sweet milk shake, or potato chips. To kids, hope is serious stuff, right smack in the middle of the main meal. Just a hunch, but I am convinced most adults would not put it there.

A Telling Telephone Call

He called from Kentucky. Having read about our recent research story about obtaining grant funding to build an artificial testicle, he wanted to know more. As a cancer survivor, he had no chance of fathering a child. He asked great questions about where the research was going and the expected time line for generating sperm from stem cells. I answered frankly as I am not a fan of dangling carrots or pipe dreams in front of others. He listened intently and thanked me kindly. I asked him to keep in touch, and that was that.

Little did he know such brief but meaningful conversations stokes my fire and fuels me to imagine, begin, execute and finish such far-fetched research projects.

Little did I know how that single, brief exchange also affected him. The next day, the Clinic received a new Yelp review (don’t get me started on this…just compare the visible reviews on the page with the invisible “filtered” accessed at the bottom). Curious, I read it. It blew me away. It went something like this (edited for brevity):

“H-O-P-E; that’s what Dr. Turek has given me; new found hope…..” After a 16-year nightmare with testicular cancer, once in 1996 and again in 2002, a good friend of mine forwarded me the most shocking, exciting, uplifting, inspiring article I had EVER read. I anxiously and carefully read it word for word, line for line, as I could not believe what my eyes were reading and my mind was comprehending. My instinct, was to call Dr. Turek’s office immediately as I was yearning for more information.”

“After talking with his office staff, a phone conference was scheduled for Dr. Turek and I within the next 3 days…Dr. Turek gave me “me” and he gave the rest of the testicular cancer world a vision that we never imagined possible… I will strive daily to do everything in my power to assist Dr. Turek in seeing this miracle discovery come to life. I will do whatever, whenever, whereever it takes to be a part of this life changing miracle. I am inspired, encouraged, and relieved with the hope of tomorrow for me and for others.”

For the first time in years, the man from Kenucky felt a ray of hope. And in some small way, his life is different today than yesterday.

Hope not Hype

So what is it about being an adult that takes the hope out of our “steak?” Why do long, strong doses of reality make it harder to dream the unimaginable? There is so much promise in hope that I, for the record, refuse to give it up. I agree with the old French Proverb that “hope is the dream of a soul awake.” You can expect more of the unimaginable out of me before my time is up on this good earth.

The Artificial Testicle: Funded!

Paul Turek, MD — Mon, 02 Jan 2012 16:00:01 +0000

Whole Earth Catalog: the old Google, according to Steve Jobs

It is the stuff of dreams in academic medicine: an NIH (National Institutes of Health) research grant. Get one of these and you’re pretty much assured of getting tenure and succeeding at any major U.S. university. It is the ultimate stamp of approval from the government and society that your thoughts and ideas have merit and value.

And I was just awarded one!

NIH Funds the Artificial Testicle

Yes, the federal grant that we submitted recently to build a human artificial testicle was funded. To be clear, this grant is not about creating a testicular implant for a man who is missing a real one. We did that a decade or so ago. This award is to develop a sperm making biological machine. I wrote it along with Dr. Connie John, CEO at MandalMed, Inc., a biotechnology company in the Bay Area. We now have a couple of years to create human artificial sperm in a dish, or more formally, a “bioreactor.” A fancy dish to be sure.

You’ve seen the posts on how successful this research has been in mice models using various stem cells as a starting point: embryonic stem cells, adult stem cells and early germ line (spermatogonial) stem cells. In labs all over the world, real, live, fertile sperm have been made in animal models from each of these stem cell precursors. Honestly, given this success over the past several years, surely we can figure out how to do the same in humans.

Why Do I Need NIH Funding?

Funny thing is, I am not in academic medicine anymore. No tenure to deal with and no need to prove anything to anyone but myself and to legions of loyal patients who depend on cutting edge innovation for their infertility care. Personally, feeling the suffering of patients with infertility is far more motivating than doing science for the sake of science, or for the sake of tenure.

Not to compare myself to Steve Jobs in any way, but I can’t help think one of his favorite mottos from the Whole Earth Catalog. This is what guided him in his quest to build a better computer for everyone: “Stay hungry; stay foolish.” It feels absolutely fabulous to be able to dream it, write it and finally to do it. The essence of science for the good of people.

Press Release

Effort to Build Artificial Testicle Awarded NIH Grant

Released: 1/9/2012 1:45 PM EST
Source: The Turek Clinic

Proposal to make human sperm from stem cells receives government funding

Newswise — SAN FRANCISCO, CA. January 9, 2012. Dr. Paul Turek, Director and Founder of The Turek Clinic, a men’s health medical practice, and Dr. Constance John, chief executive of MandalMed, Inc, a San Francisco-based biotech company, were recently awarded a Small Business Innovation Research (SBIR) grant from the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) to construct an artificial human testicle and research how sperm are made from stem cells.

“Fertile sperm can be made from various stem cells in mice, but making human sperm from these same sources has been elusive,” says Turek, a practicing male infertility specialist in San Francisco. In this project, they will try to produce mature human sperm in a live laboratory model of a human testicle.

This work extends on previously published research by Dr. Turek on human testicular stem cells, the forerunners of sperm. Dr. John is an expert on human Sertoli cells, which critically nurture sperm as they develop in the testicle. “This grant is quite an honor and comes after several years working together on this idea,” notes Turek. “We have assembled a great group of scientists who are very committed to its success.”

A functioning artificial testicle has important implications for the field of reproductive biology. It could shed enormous light on the intricate details behind the mysterious and complicated process of spermatogenesis or sperm production. Even further, it could be used to later develop patient-specific, fertile sperm for men who simply do not make sperm due to genetic or acquired causes.

About Paul Turek, MD
Paul Turek, MD is founder of The Turek Clinic and a former professor and endowed chair at the University of California San Francisco. As a men’s reproductive health expert, he has pioneered innovative techniques for treating male infertility, including Testicular Mapping. In addition to his appointment to the Cooperative Reproductive Network Advisory Board, Dr. Turek sits on the Advisory Board for the Men’s Health Network, Fertile Hope and is President-Elect of the Society of Male Reproduction and Urology. He is Chief Medical Officer at MandalMed, Inc, and is also Past-President of the American Society of Andrology and of the Northern California Urology Society and is an Editorial Board member of several journals including Systems Biology in Reproductive Medicine, the Asian Journal of Andrology and the International Brazilian Journal of Urology.

A complete biography of Dr. Turek is available on Wikipedia at http://en.wikipedia.org/wiki/Paul_J._Turek.

About The Turek Clinic
The Turek Clinic, founded in 2008, is a men’s reproductive health practice specializing in male infertility, vasectomy, vasectomy reversal, varicocele repair, and other minimally invasive procedures using innovative and cutting-edge techniques. For more information, visit www.TheTurekClinic.com, www.TurekVasectomy.com, or Dr. Turek’s blog (here).

About MandalMed, Inc.
MandalMed is a privately held biotechnology company located in San Francisco- the home of more bioscience companies than any other region in the world. MandalMed’s mission is to develop pharmaceutical products of worldwide significance. Areas where there is a great need for better treatments, including cancer and neurological conditions, are the targets of MandalMed’s research and development programs. For more information, see www.MandalMed.com.

An Ounce of (Fertility) Prevention

Paul Turek, MD — Mon, 17 Oct 2011 15:00:19 +0000

Kokopelli, the ancient fertility symbol.

“I’ve been told that my cancer is now cured… how do I get my fertility back?

Patients ask me this question weekly all the time and I am glad to help. Some of the most satisfying medical moments I’ve had are associated with these patients.

But when I hear this call for help, it also reminds me how medicine has been remiss in preventing the infertility in the first place. We can do better and we can do it right now.

The topic of fertility preservation is the substance of my recent lecture at the annual meeting of the American Society of Reproductive Medicine (ASRM) in Orlando, Florida. This well-attended course focused on the prevention, treatment and restoration of male fertility in the setting of sterilizing treatments typical of cancer therapy.

The goal of my lecture was to review and update providers on current and future strategies for the preservation and restoration of male fertility. Here are some of the ideas discussed. I’ve also included a link to the lecture slides if you are so inclined.

Preserving Male Infertility

Sperm banking. A 200-year old technique that is the purest form of preventative medicine, it is vastly underutilized, not covered by insurance, and not routinely offered to many cancer patients before treatment. What gives? Here is where we need to do the most work in this field.
Sperm Harvest. For 15 years, it has been possible, nay routine, to harvest sperm from men who want children after having a vasectomy without reversing the vasectomy. This same technology is easily applied to men before, during and after sterilizing cancer treatments. One very successful example of this in my practice is fine needle aspiration “mapping” of testicles for sperm in cancer survivors. Indeed, no-touch, metabolic imaging for sperm may be the ultimate iteration of this concept.
Electroejaculation. Based on decades of successful use in spinal cord injured men, artificial stimulation of ejaculation can be a very effective way to bank sperm or restore fertility in men or post pubertal teens who have had nerve damage to reproductive organs from cancer surgery.
Shielding Sperm Production. Physical shields are routinely used to block the effects of aberrant X-rays from hurting sperm production during treatment. In animal models, hormonally induced shut down of sperm production can protect the testicle during the storm of chemotherapy as well.

Restoring Male Infertility

Stem cell transplantation. Currently possible in animal models, this involves taking the delicate testicle stem cells from either pre- or post-pubertal boys or men and freezing the cells before cancer treatment. Subsequently, the stem cells are thawed and replaced back into the testicle to restore sperm production after the cancer is cured.
Sperm Maturation in a Dish. A variant of the above, also demonstrated in animal models, this technique involves maturing stem cells harvested from the testicle before cancer treatment in the laboratory all the way to their final form: a sperm with a tail.
Sperm from Stem Cells. Yet another variant of the above that has been demonstrated in animals, this involves growing usable sperm from early, pluripotent stem cells such as embryonic or adult pluripotent stem cells. One example would be to take a skin biopsy from a sterile man, coercing them to become adult stem cells and then push those cells to sperm in a dish. Truly, a fantastic outcome of America’s investment in stem cell technology.

Fertility Restoration after Cancer: Current and Future Therapies by Paul J. Turek MD, FACS, FRSM Director, TheTurek Clinic, San Francisco (WARNING: Images in slides not appropriate for all audiences due to subject matter)

View more presentations from Dr. Paul Turek | The Turek Clinic

Mice Sperm in a Dish

Paul Turek, MD — Sat, 09 Apr 2011 15:11:11 +0000

If they just would have included a photo of the finished product…

It’s not the mother load of discoveries in our field, but it’s pretty close. It tells us that the mother load is definitely out there…and within reach. Yup, the good news is that real. live, old-fashioned sperm were made in a dish… at least for mice.

The Holy Grail: Artificial Sperm

For the 55,000 reproductive age cancers survivors annually in the U.S. and a host of other men who are sterile due to injury, genetics, exposures and the like, this is good news. Despite the availability of utterly fantastic reproductive technologies like sperm mapping, in vitro fertilization and intracytoplasmic sperm injection, some men still do not have sperm to use them. The standard of care in reproductive medicine today is a sperm: a mature one, with a tail, and hopefully moving or at least alive.

And the sperm can come from anywhere. Often, men with no sperm in the ejaculate will have sperm within the reproductive organs such as the testicle or epididymis. These sperm work great to help them become fathers. But there are many other men do not have any sperm, anywhere, especially men with childhood cancers who were blasted with sterilizing treatments before they even reached puberty and made their first sperm. Clinically, I see these patients all the time and this is the crowd of men I am very motivated to help in my short time on this good earth.

The Finding: Functional Sperm for Mice

The recipe to produce functional sperm from stem cells precursors has eluded researchers for 50 years. There have been many false starts, including the last one in 2009 out of Newcastle that was published and then retracted from print by the editors one week later. But, a group from Yokohama City Japan nailed it and recently published functional mouse sperm from testis stem cell precursors.

From reading the paper, it is clear that it took several years of constant, diligent work to find the key ingredients to make it happen. In my opinion, the secret sauce was that our recent, vastly improved understanding of stem cell biology really enlightened the science. They took testicular tissue from newly born mice that contained only stem cells (no sperm, just sperm precursors) and put them in a jello-like environment. Getting them to grow was the trickiest part and finding the right food was also critical.

How is This Sperm Different?

What made this paper great was that the scientists made reproductively “competent” sperm. They took the artificially created sperm and used them with high technology approaches to create baby mice. Then, they let the baby mice grow up and mate. Remarkably, the offspring of these mated mice were normal. Can’t ask for much more from a sperm now can we? Many have tried, including some of my closest colleagues, but no one has gone this far before. Bravo!

So now, all we have to do is replicate this in humans, something that I have been pursuing for several years with colleagues. What is so uplifting for me about this paper is that it seems that making human sperm in a dish is really more evolutionary than revolutionary science. I better go buy some more of that midnight oil….

Giving Up the Gavel

Paul Turek, MD — Sat, 02 Apr 2011 14:07:43 +0000

A gavel with teeth for this President…

In two days, I will hand over the gavel. It’s actually a meat tenderizer that I bought to run the meetings this year and it worked just great. A gavel with teeth. Regardless, I surrender it with mixed feelings. On one hand, a year as President of one of America’s leading academic societies is a lot of work. On the other, though, I feel like I am just getting started and that the ship is now running fast with sails full. As we all know from politics, systems with rotating leadership all have their virtues and vices.

The American Society of Andrology

The Society that I lead is the American Society of Andrology. It was founded in 1975 and has about 700 members, most of whom are academic researchers. I guess I have a soft spot for nerdy scientists who care about men’s health. Honestly, though, this group is unique. This week’s annual meeting in Montreal brings together a top-notch group of scientists and clinicians from around the world whose expertise, interest, friendship and collegiality lend to a remarkable cross-fertilization of science and medicine.

What the Heck is Andrology?

My mother still asks me this question. Andrology is the study of men’s health and, in particular, the male reproductive system. It involves all aspects of reproductive fitness, including fertility and infertility, erections, hormones and sexuality. As a reflect upon the Society’s position in the academic world, my elevator pitch is that this Society’s focus is on “The Science of Men’s Health.”

President’s Tribute

The year has been a good one: restoring falling membership, bringing financial stability, initiating a strategic plan and an endowment campaign, and brokering the merger of the Society’s academic journal with that of its European counterpart, the European Academy of Andrology, to ensure its future livelihood.

But, as with most endeavors, the people make the party and I must admit, my colleagues rose magnificently to execute the demanding projects that I put forth this year. And this means a whole lot. In fact, this and only this is substance of my final toast, a limerick, at the Welcome reception tonight. I probably shouldn’t leak it here early, but for you dear reader I submit:

There once was a crazy society,
Subscribed to by much notoriety,
Its goal, so sincere,
To study things dear,
Like sex, with the utmost sobriety.

But not only sex does it foster,
There is but a much longer roster:
Like sperm, prostate, erections,
And most epididymal sections,
And diseases like clap and zoster.

And don’t forget contraception,
The inimitable acrosome reaction,
And ejaculation that’s early,
With low libido that’s surely
A sign of hormonal malfunction.

So as we meet here in old Montreal,
Let’s remember these orders so tall:
To discuss, think and debate,
With friends old, new and irate,
The science to which we are called.

The Orchid in the Arctic

Paul Turek, MD — Sun, 31 Oct 2010 05:19:55 +0000

Hard to find an orchid in the arctic.

Imagine taking a tiny skin biopsy from the arm of a man who, even while you are taking it (which can’t be pleasant) offers you a warm, reassuring smile. For this man, getting poked and prodded is nothing—he is happy enough just to be alive and breathing. A second chance at life after surviving cancer and its exhaustive therapy puts things into perspective.

The biopsy doesn’t bother him at all, as he really wants to be a father and you, by doing this, can help him achieve this lifelong goal. How? By turning those skin cells into sperm with his DNA inside…and all in a dish. A complex dish. And then, using those sperm with current reproductive technology, his wife will conceive their child. And you will get a holiday card with a short but heartfelt note every year for the rest of your life.

Is this reality? No. At least not yet. But this past week, I presented a paper at our international fertility meetings in Denver that suggests that this is more like a workable vision than a pipedream.

In this research paper, we revealed that we were able to isolate, maintain and grow in a dish a support cell that is critically important for normal sperm production in all mammals. These particularly squeamish and elusive cells, called Sertoli cells, are the “nurse” cells of the testicle and provide total environmental support for early testis germ line stem cells to develop into sperm. Think of a seed trying to grow into a plant without nurturing soil. It’s just not gonna happen.

For 30 years, scientists have grown Sertoli cells from other animals in a dish, but human Sertoli cells have been elusive to date. Like trying to grow orchids in the arctic cold. What made this research successful was thinking about this cell differently than we had been. Adding a dash of stem cell biology also helped.

Stem cell biology has taught us that if you take cells out of their normal “niche” or home, they behave differently. Put a Sertoli cell into the testis with all of its friends and the things it calls home around it and it will stop dividing. “Terminally differentiate” in medspeak. Take it away from home and put it in a dish instead and low and behold, it continues to grow and divide and duplicate itself. And although it may be lonely away from its niche, it can now be used to help us build an artificial testicle to treat male infertility, study how sperm are made, and to test the toxicity of new drugs without using animals.

So that’s what the Smiling Man is smiling about. His skin cells will be converted to stem cells that will be converted to sperm in an artificial testicle in a dish. We now have the soil and the seed. Stay tuned as we work on the water and sunlight to turn this seed into a breathtaking orchid.

Your Oldest Treasure

Paul Turek, MD — Mon, 19 Jul 2010 04:15:46 +0000

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.

Stem Cells are People Too

Paul Turek, MD — Sun, 14 Mar 2010 23:37:28 +0000

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…

Keeping the Family Jewels Shining

Paul Turek, MD — Sat, 02 Jan 2010 18:47:05 +0000

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!

No Men. Just Sperm.

Paul Turek, MD — Thu, 09 Jul 2009 19:17:24 +0000

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?

How Are Stem Cells Like Wine Grapes?

Paul Turek, MD — Wed, 27 May 2009 00:57:53 +0000

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.

Stem Cells, Snake Oil and You

Paul Turek, MD — Mon, 18 May 2009 15:19:10 +0000

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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