If a 6-year old boy must take cancer chemotherapy and will likely become infertile, no techniques are currently available that help him have genetic children in the future. For adults, sperm-banking is the option but it is not an option for prepubertal and adolescent boys. This is an important quality of life issue to the patient himself, but also to the patient’s family and his future partner. I investigate sperm-producing stem cells (spermatogonial stem cells, SSCs), which exist from the time of birth and throughout life, and critically, these cells provide an irreplaceable resource to preserve fertility of boys and men at any age. We expect that SSCs can be harvested from a patient before therapy, and following cryopreservation, transplanted back to the patient, resulting in the production of his own sperm. This scheme has already been realized in animal models. Why not with humans? This is our research goal.
Our current research focuses on three critical issues in SSC research.
First is to generate a fate map of SSC commitment in mice and humans. We ask, what are the steps of SSCs commitment to differentiation until they lose their stemness, and what occurs during the process? Through these efforts, we eventually want to “see” SSCs with our own eyes, which no one has been able to do since the first SSC concept proposed in 1885. Over several years, we have accumulated the abundance of important data using flow cytometry and the SSC transplantation assay. We can now purify mouse SSCs to the level that has not been reported before without using a transgenic marker gene or modifying cells in any way. We are currently analyzing single cell transcriptome data and hope to report our finding in the near future. A glimpse of this research activity can be seen on a YouTube video.
The second area is to develop novel technologies to increase the SSC homing efficiency after transplantation. We collaborate with developmental biologists, clinical andrologists, and chemical engineers at McGill and have been designing and producing novel compounds in order to allow for more SSCs to engraft and regenerate spermatogenesis after transplantation. We envision that our new approach should make the restoration of male fertility after SSC transplantation more efficient and effective. The animal testing phase is near completion and we plan to move on to preclinical human studies.
The third area of our research is to apply human SSCs to clinical settings, including developing a reliable and reproducible human SSC culture to expand them and assess their genetic and epigenetic integrity during the culture period. We also believe that our first research aim (fate map) is a very essential research process to realize human SSC propagation in vitro, which has not been successful. For this aim, we collaborate with clinicians at the MUHC and researchers at the University of Pittsburgh
The Nagano lab constantly looks for new lab members, the enthusiastic people who are full of curiosity for nature, biology, and the mystery of creatures with whom we cannot share a language. At the level of postdoc, grad students, research assistant, or lab technician. If you are interested, please email me at makoto.nagano@mcgill.ca.
