Can skin be turned into sperm? The answer is “yes” in mice and “almost” in man. Yup, we are one small step closer to the holy grail of making sperm from stem cells. And this time, it looks like it might happen using stem cells that are widely available for men.
What’s the Buzz?
You know that I am obsessed with helping men who have no sperm become biological fathers. When FNA mapping yields no testicular sperm, I ask men to do what they have to do to keep moving forward…but to stay tuned to the research advance as well. Honestly, I consider our latest published research a significant “moment” in the sperm-from-no-sperm continuum. And, it hinges on the great potential of good ole’ stem cells.
Where’s the Beef?
In this study, we took tiny skin biopsies from generous patients who were deemed, by the latest and greatest techniques such as sperm mapping, to have no testicular sperm. They also had good reason for their circumstance: each harbored a genetic issue called a Y chromosome microdeletion.
Then, using Nobel Prize proven technology, my collaborators at Stanford University cleverly converted these adult skin cells into stem cells. A cool, and now old-school technique in stem cell science. They then transplanted these adult stem cells into mouse testicles to see what they would do within a relatively natural and ready-made, “live” testicle. You see, stem cells like to “fit in” and typically respond to their environment or “niche” and develop into cells that suits their surroundings. When mouse stem cells are placed into mouse testicles, they develop into germ cells and, eventually, sperm. But, would human sperm develop in the mouse?
Putting human stem cells into mouse testicles, though, presents an unusual challenge. Because of obvious evolutionary divergence between mouse and man, human sperm have never been made in the mouse. So, we did not expect to see human sperm develop in this model. And we didn’t. But what we did find was both exciting and surprising:
- Skin-derived stem cells from profoundly infertile men gave rise to early germ (sperm precursor) cells in mice, similar to cells from fertile men.
- The degree to which infertile men made early germ cells in the mouse testicle was 5-10x less efficient than that observed with fertile men.
- Stem cells that missed the testicular tubules and were found outside of the correct “niche” developed into tumors at high rates. Not good but important to know.
This research suggests that even men with the severest forms of infertility may actually start life with a precious few functioning germ cells, which they then lose as they age, resulting in sterility as adults. That, my friends, opens up an opportunity where there was none before. In addition, it suggests that cells other than embryonic stem cells (the mother-of-all stem cells and entirely unavailable to men) might be used to make sperm in the future. Another opportunity. Lastly, it tells us that the stem cell “niche” (here a mouse testicle) is indeed a powerful place that, if engineered just right, might allow us grow a patient’s sperm from stem cells in the future. Could our artificial testicle be that place? We’ll simply have to wait and see…