Many of our sperm bank patients are young men recently diagnosed with cancer. Chemotherapy and radiation therapy put these men at risk for permanent infertility as both treatments kill off sperm cells along with cancer cells. Some of these men will eventually regain the ability to produce sperm after the cessation of treatment, but many unfortunately will not. Cryopreserving sperm prior to starting treatment provides adult male cancer patients with a way to preserve their fertility and father their own biological children in the event their sperm production does not rebound after treatment.
However, not all male cancer patients are old enough to produce sperm, so sperm cryopreservation is not an option for fertility preservation. As a matter of fact, right now there are no proven options available for pre-pubertal males to preserve their fertility, which can be very distressing for their families. Fortunately researchers are working hard to end this dilemma. They are using cutting edge stem cell technologies to develop fertility preservation options for pre-pubertal boys. Our facility, in fact, is one of only a few reproductive tissue banks in the country that has an approved research protocol that allows banking of testicular tissue from pre-pubertal boys for potential use in the future……read on.
The cells of the human body are highly specialized depending on their designated function. This means they have developed specialized structures that enable them to carry out a specific function in the organ system to which they belong. A nerve cell (neuron) has dendrites and an axon to enable it to transmit nerve impulses. A sperm cell has a flagellum (tail) and a lot of mitochondria (energy production) to enable it to move through the male and female reproductive tracts. A stem cell is a cell that has not yet undergone this process of specialization (cell differentiation). Mature sperm start out as spermatogonial stem cells (SSCs) in the basement membrane of seminiferous tubules in the testes. Men of all ages, newborn to ninety, have spermatogonial stem cells (SSCs).
Researchers are developing several techniques for generating mature sperm from spermatogonial stem cells (SSCs). This would mean that testis tissue containing SSCs could be surgically extracted from a pre-pubescent male cancer patient prior to the start of his treatment. The tissue would be cryopreserved and stored. At a later point in his life, the tissue would be thawed and the appropriate stem cell therapy would be used to generate mature sperm cells from the SSCs, thus enabling the patient to achieve a pregnancy with his partner. Our approved protocol allows us, after obtaining an informed consent from the patient and/or patient’s parents, to store testicular tissue for potential use of their own stem cells that may be present in the stored tissue.
Researchers are exploring several different methods of using spermatogonial stem cells (SSCs) to generate mature sperm. The first is to transplant the SSCs back into the testes when the patient is past puberty. “For this approach, an injection needle is simply inserted under ultrasound guidance through the scrotal skin and testicular parenchyma (working tissue) into the rete testis space”. The transplanted SSCs would regenerate spermatogenesis, producing mature sperm and restoring fertility. This method has been successfully tried on rhesus monkeys. The downside to this technique is it potentially runs the risk of reintroducing cancer cells into the patient, and testis tissue samples typically contain a very small number of SSCs.
The second method being developed by researchers involves culturing spermatogonial stem cells (SSCs) before transplanting them into the testes. Culturing means growing cells or tissue under controlled conditions in a laboratory. Culturing SSCs enables researchers to increase the number of SSCs that are transplanted. It also allows researchers to determine whether or not cancer cells are present. Further work is needed to develop the best culturing media and techniques, and to evaluate if the resulting stem cells function properly.
Rather than isolating spermatogonial stem cells (SSCs) for transplantation, some researchers are working with grafting testicular tissue under the skin of mice. The SSCs in the grafted tissue mature into sperm that can be retrieved and used in IVF/ICSI. This technique has been successfully tested using fresh testis tissue from newborn pigs, mice, and goats. Trials using cryopreserved tissue have been unsuccessful in producing mature sperm – maturation is arrested at an early stage of sperm development. Obviously this glitch needs to be addressed before testicular tissue grafting is to be a fertility preservation option for pre-pubescent male cancer patients.
Researchers have been able to generate mature sperm from testicular tissue organ culture. Testis tissue from baby mice containing only SSCs has been cultured, generating mature sperm that have been used in ICSI resulting in normal offspring. Cryopreserved and thawed tissue has been successfully cultured to produce mature sperm. Sperm generated from cryopreserved and thawed tissue however has not yet been tested to determine fertility potential (ie can it achieve pregnancy).
I know for some readers, the concept of using stem cell therapies to generate mature sperm may seem “off in the distant future”, but many in the scientific and medical communities would firmly disagree. As discussed earlier, or facility has applied for, and obtained, Institutional Review Board (IRB) approval to cryopreserve and store testis tissue from pre-pubescent male cancer patients, as our director believes that stem cell therapies will exist to enable these patients to use this tissue to father their own biological children, should the need arise. The future is truly almost here, and the families of pre-pubertal male cancer patients should be informed of the potential fertility preserving benefit of cryopreserving and storing testis tissue prior to starting chemotherapy or radiation treatment.
Valli H, Philips BT, et al. Germline stem cells: toward the regeneration of spermatogenesis. Fertil Steril, Jan 2014; 101 (1): 3-13.
Stem Cell Information, from http://stemcells.nih.gov/info/basics/Pages/Default.aspx0