Long-term survival of human spermatogonial stem cells in mouse testes.
OBJECTIVE
To evaluate colonizing ability of human spermatogonial stem cells in mouse testes.


METHODS
Transplantation of human testis cells into the seminiferous tubules of immunodeficient mice.


METHODS
University hospital and academic laboratory.


METHODS
Men with obstructive azoospermia or maturation arrest of spermatogenesis. Analyzed up to 6 months after transplantation. Also analyzed: cryopreservation of donor cells, donor cell concentrations, and leuprolide treatment of recipients.


METHODS
Detection of human donor cells in recipient testes using whole-mount immunohistochemistry with antibodies that react with human germ cells.


RESULTS
Mouse testes were colonized by human testis cells obtained from each of 6 patients; overall, human spermatogonia were found in 16 of 22 (73%) recipient testes. Human spermatogonial stem cells survived in mouse testes for at least 6 months and proliferated during the first month after transplantation. No human-differentiating spermatogonia were identified, and meiotic differentiation did not occur in mouse testes. In this initial study, human stem cell colonization was not influenced by cryopreservation of donor cells, donor cell concentration, or leuprolide treatment of recipient mice.


CONCLUSIONS
Xenogeneic transplantation of human germ cells using mice as recipients is feasible and could be used as a biological assay system to further characterize human spermatogonial stem cells. This study might provide a mechanism to evaluate the status of the stem cell population in selected infertile male patients.
Nagano
Makoto
M
Department of Animal Biology, School of Veterinary Medicine., University of Pennsylvania, Philadelphia, Pennsylvania 19104-6009, USA.
Patrizio
Pasquale
P
Brinster
Ralph L
RL
D000328:Adult; D000818:Animals; D002470:Cell Survival; D016922:Cellular Senescence / Q000502:physiology; D003114:Colony-Forming Units Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009845:Oligospermia / Q000473:pathology / Q000503:physiopathology*; D013091:Spermatogenesis / Q000502:physiology; D013093:Spermatogonia / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*; D013737:Testis / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014183:Transplantation, Heterologous