Turek On Men's Health » Adult Stem Cells

The Incredible (Renewable?) Egg

Paul Turek, MD — Mon, 05 Mar 2012 18:32:47 +0000

The human egg: a thing of beauty…now a renewable resource?

It’s hard to keep up anymore; things are changing so quickly in fertility medicine. Just in the last week, a Harvard researcher discovered stem cells in the human ovary and a 66 year old just became a mom to twins in Switzerland. There goes the rug, being pulled out from under our scientific feet yet again.

Testicular Stem Cells

A couple of years ago, we published a paper confirming the presence of cells in adult men that were long though to exist: testicular stem cells. These are “multipotent” cells unlike most other cells in the body: they not only renew themselves, but they can also become sperm and may even be coaxed into becoming other organs in the body. The really convenient thing is that they are not derived from embryonic stem cells (a political minefield) a fact that makes them prime candidates for stem cell-based treatments in the future.

The Dogma About Eggs and Ovaries

But eggs are not sperm. Sperm are made constantly throughout a man’s life, like blood cells, and therefore it makes sense that there are stem cells running the show. However, for at least as long as I have been in medicine, it has been thought that women are born with all of the eggs they will ever have, some 1-2 million, and lose them throughout life, most obviously through monthly ovulation, until they are gone. The basket empties of eggs somewhere in the 40’s for most women, about 10 years before menopause. This lack of new egg production has led to the belief that, unlike within the testicle, adult stem cells do not exist in the ovary.

Ovarian Stem Cells

But Dr. Jonathan Tilly at Harvard thinks otherwise. He believes that women indeed have adult stem cells in the ovary that might be able produce new eggs during a woman’s lifetime. And maybe even after her traditional reproductive window has closed.

Dr. Tilly first showed this in mice and published it in 2004. He recently extended this work to women by locating an incredibly scare biological resource: fresh ovaries donated by Japanese women undergoing sex change procedures. Within this tissue, he found cells that showed classic stem cell characteristics using genetic markers. But this only means that they “look” like stem cells. To prove that they can “act” like real stem cells, he isolated these cells in a Petri dish and watched them turn into real, live, immature eggs. More convincingly, he then transplanted them into mice and they continued to develop into even more mature eggs, passing through meiosis in some cases which is a characteristic process occurring only in eggs and sperm.

So what are the implications of this technologically mind-bending work? Hard to know, but down the line it may mean that women may be able to make new eggs when we thought that they couldn’t. Maybe their baskets never really empty of eggs and that their fertility can be extended beyond what we now think is possible.

Regarding the 66 year old women who just had twins…it’s not clear to me how many genetic parents were involved, how long it took, and how heroic the effort was, but I can guarantee you that she will have her hands way too full for the next several years to keep up with this science.

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 Recipe for Man Made Sperm

Paul Turek, MD — Mon, 08 Aug 2011 15:00:32 +0000

Will stem cell "recipes" become as tried and true as the ones in this book?

Stem cells rock. While the stock market tumbles, stem cell science is sizzling. I know, you’re thinking: what is he talking about? No diseases have been cured with new stem cell technologies. But, from what’s being discovered almost weekly now, I can tell you that male infertility is likely to be one of the earliest boxes ticked on the “Diseases to Cure” list for stem cells.

Sperm from Stem Cells

Honestly, stem cells appear to be great to use to create sperm. Just a few posts ago, I shared the exciting findings from a group in Japan who took stem cells from newborn mouse testicles, placed them in an “organ culture” system (basically Jell-O), and grew mature, fertile sperm in the laboratory. Over the past 2 years, my colleagues at Stanford have also shown that human embryonic stem cells can be pushed along the path toward sperm in a dish. They also showed that adult stem cells from places like skin can also be driven in the same direction. Not all the way to mature sperm, but certainly more than half the way.

Overcoming Sterility in Mice

Last week, researchers at Kyoto University in Japan brought man made sperm closer to reality…at least in mice. I know many of you aren’t really worried about infertility in mice, but we have to start somewhere.

In a study published this past week, they took embryonic stem cells from mice, the mother of all cells, and watched them closely as they began to develop into other cell types (i.e. differentiate) in a dish. After several days, they plucked out rare and transient downstream stem cells called the primordial germ cells and transplanted these cells back into sterile baby mouse testicles. And sperm were made. Good sperm. Genetically intact and fertile sperm. Sperm that led to offspring that were also naturally fertile. And they did the same experiments with adult stem cells and got the same result, eliminating the need to use embryos at the start.

Please realize that this success did not happen overnight, but was the result of good, wholesome science and lots of sweat equity. And not all the results were rosy: primordial germ cells are rare, short lived and inefficient. In addition, when slightly different cells were injected into testicles, benign tumors formed, the scourge of stem cell science. So now you understand why mice experiments come first.

Stem Cells and Human Male Infertility

Imagine this: A boy has cancer and gets cured by being pounded with chemotherapy. Easily enough treatment to sterilize him for life. After that, his testicles could make sperm, but the “seeds” (early germ cells) that develop into sperm have been wiped out. Solution? A skin biopsy. Turn it into an adult stem cell and inject it right back into his testicles. And ta da! Sperm. I can’t stop thinking about how possible all of this is, as stem cell recipes are perfected. As Ted Allen, The Iron Chef once said: “There are two words to improve any dish: Ba-Con.”

Timing (And Position) Are Everything

Paul Turek, MD — Mon, 18 Jul 2011 15:00:39 +0000

Does timing and position matter for sex like it does for surfing?

Missionary? Doggie? Cowgirl? Kneeling Lotus? Quarter moon? Full moon? No moon? Is there really a best lovemaking time or position to have a girl or boy?

History of Designing Sex for a Boy or Girl

Methods for determining baby gender are ancient, even prehistoric, and range from astrological, to dietary to positional. One of the earliest references to this concept is the Chinese Birth Gender Chart, said to have been discovered in a tomb near Beijing for where it lay for 700 years. It supposedly now resides in the Institute of Science in Beijing. It claims to predict the sex of the child from the month of conception and the age of the mother.

It has also been said the many myths about sex position and timing determining baby gender resulted from the mad rush of lovemaking that followed the end of the World Wars and the return home of soldiers. I’m sure this influx of war torn yet triumphant, and testosterone laden yet depraved men gave new meaning to the term “Honey, I’m home!” for many mid-century modern couples.

The Lovemaking Myths

Here are the most common myths regarding sexual position and timing to help get that boy or girl. Sorry, no pictures. I hear these from patients all the time, as they look at me bright eyed, with heads nodding, searching for my blessing.

Eat meat and salty food to get a boy.
Splurge on desserts to get a girl.
Both partners eat lots of fish and vegetables for a girl.
Make love standing or doggy style and during a quarter moon or at night for a son.
Use the missionary or cowgirl position and during a full moon for a daughter.
The Shettle method suggests having sex as close to ovulation as possible, for a boy, as boy sperm are less robust than girl sperm. Do the opposite for a girl.
If the male partner climaxes first, then a boy will be conceived. The opposite is suggested for a girl.

The Lovemaking Truths

Sorry to be the bearer of bad news. Despite all that you may have heard, there is no real data supporting the idea of a “best” position or time for sex to conceive a boy or girl. In fact, a prospective study of couples starting to conceive was actually published in 1995 in the New England Journal of Medicine that reported no relationship between the timing of intercourse and baby gender. Ah, but they did not study lovemaking position, thus keeping that myth and folklore alive! Come to think of it, that would be an interesting study to do, and one that I imagine would have no trouble enrolling subjects…

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…