Q from U: Is testicular stem cell transplantation real or a hoax?

April 11, 2013Carole 2 Comments »

Recently, I received this question from a blog reader, ” I want to ask you about testicular stem cell transplantation– is it true or hoax?”. The short answer is, “No, it is not a hoax, but it is not a clinical treatment yet either”.  I found this review article, Restoring Fertility in Sterile Childhood Cancer Survivors by Autotransplanting Spermatogonial Stem Cells: Are We There Yet?“,  which does a very nice job of explaining why anyone would first, be interested in transplanting testicular stem cells and two, what hurdles stand in the way of this clinical treatment.

To understand this, it is important to consider the problem of childhood cancers. We are getting better at curing childhood cancers so that the life expectancy for some survivors of childhood cancers is well into adulthood and even old age. This increasing longevity makes one of the possible side-effects of life saving chemo and radiation therapies-namely, sterility–a quality of life issue. Although some cancer survivors can recover some or most of their sperm production ability, other male survivors are irreversibly sterile after treatment. It is not possible to exactly predict in which category a person may find themselves in the future. The type of cancer and intensity of the treatment used both affect the probability of becoming sterile.  For teenage boys who have gone through puberty and adult men, it is possible to collect one or more ejaculates before cancer treatment, and freeze and store these samples for future use, as a sort of “insurance policy”  against sterility.  For pre-pubertal boys, this is not an option because they aren’t producing sperm yet.

But pre-pubertal boys have lots of testicular stem cells called spermatagonial stem cells (SSC) which could in theory, be likewise recovered and saved  before cancer treatment and returned to the testicles later to repopulate the testicular tissue with sperm-producing cells.

SSC are the renewing stem cells whose job is to replicate themselves so that there is a continual stem cell supply (see Type Ad Spermatogonium (the blue cells) in a renewal cycle below). Not all stem cells replicate themselves. Some commit themselves to a differentiation pathway that ultimately results in the mature sperm cell (right handed pathway- with multi-colored cells).  http://upload.wikimedia.org/wikipedia/commons/d/d4/Spermatocytogenesis.pnghttp://upload.wikimedia.org/wikipedia/commons/thumb/b/bb/Germinal_epithelium_testicle.svg/200px-Germinal_epithelium_testicle.svg.png

There are multiple steps after the secondary spermatocyte stage. The spermatocyte cell loses its round cell shape and begins to look like a sperm  in a process called spermiogenesis.  The cell elongates, gets a tail, puts it mitochondria behind the sperm head, loses excess cytoplasm, encapsulates the DNA in a proper sperm head etc. At puberty, some of the stem cells spring into action and start making sperm. A helper cell in the testis called the Sertoli cell (shown as the pinkish cells studded with blue spermatocytes- the smaller figure above) serves as a sort of docking station through which the spermatocytes pass as they morph into a proper sperm cell.

So how would gonadal cell stem cell transplantation work?

Step One: Under anesthesia, take a testicular biopsy. Freeze the biopsy and store for future use.

Step Two: Thaw tissue sample when the patient is in remission and is ready to start a family.

Step Three:  Inject a suspension of thawed testicular cells containing stem cells into the rete testis of the patient, where hopefully the stem cells will seed and re-activate to produce more of themselves and then many, many sperm cells.

Other proposed fertility preservation options using stem cells which one day may have clinical applications include:

  • Grafting testicular tissue back into the testis. Tissue could be derived from frozen/thawed specimen or possibly donor tissue.
  • Putting testicular stem cells in culture and growing out sperm cells from these stem cells in a dish. The number of sperm produced would likely be enough only for IVF or ICSI, not uterine insemination.
  • Make more stem cells-and then sperm- from non-gonadal cells, by reverse engineering the pathway from more differentiated to less differentiated (stem cell)  and then committing the stem cell to make a more differentiated (sperm cell). Sperm was produced from embryonic stem cells (and in another experiment, fibroblast cells) in the mouse by first making induced testicular stem cells and then making those newly derived stem cells into sperm. These sperm were used to make mouse pups.

Hurdles to these approaches are not insignificant.

  • We do not presently have a good method to propagate or amplify the rare stem cell recovered from a patient’s testis into significantly more stem cells in vitro. We also want to be certain that when these cells divide in culture that they remain”true” to the original copy and aren’t introducing genetic mutations because they are more unstable than “wild type” cells. We need to understand stem cells better.
  • There is always a possibility when removing cells from a cancer patient, that you recover some contaminating cancer cells along with the normal healthy cells, even if the cancer is not in the testicle. If it is in the blood, there is some theoretical risk of transplanting the cancer. This would obviously be a catastrophe. We must figure out ways to minimize this risk but we are not there yet.
  • If all the technical barriers were overcome, and it works, and we have babies born from these stem-cell transplant procedures, what assurances could we have that children born from these procedures will be as healthy as children in the rest of the population? Obviously, at the very least, we would want to do many generations of studies in animals first.

So although there is a long way to go, stem cell transplantation is a real area of research, not a hoax. Someday, it may even be a standard clinical procedure for fertility preservation in the pre-pubertal male who is at risk of sterility due to cancer treatment.

 

© 2013, Carole. All rights reserved.

2 Responses to this entry

  • Brooke Says:

    Thanks for sharing your thoughts on testcular transplantation.
    Regards

  • Brenda Says:

    I have long suspected that cell phone (and now lotapp) usage has been a troubling health effect. Germany has done some very intriguing studies on these very problematic issues. Sadly these devices have the potential to cause more harm than infertility alone. Just do a google search and you’ll see what I am talking about. I read many years ago about the difficult consequences particular devices, especially wireless gizmos can have from prolonged use. If cancer isn’t a wake up call, I don’t know what will be; the problem is that the corporate titans of the world are manipulating the truth on a massive scale. People have no idea the lengths these mega giants have gone to to deceive society from these scary facts.

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