Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog

Kim, Yeunhee; Turner, Danielle C.; Nelson, Jacquelyn L.; Dobrinski, Ina; McEntee, Margaret C.; Travis, Alexander J.

doi:10.1530/rep-08-0226

Cited by 112 publications

(92 citation statements)

References 45 publications

(67 reference statements)

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“…Brinster and colleagues provided the initial demonstration that testicular cells from a fertile mouse could be transplanted into the seminiferous tubules of an infertile recipient, in which they produced complete spermatogenesis and sometimes restored fertility (12)(13)(14). Regeneration of spermatogenesis following SSC transplantation has now been established in several animal models, including rodents, goats, sheep, pigs, dogs, and monkeys (13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Eliminating malignant contamination from therapeutic human spermatogonial stem cells

Dovey¹,

Valli²,

Hermann³

et al. 2013

J. Clin. Invest.

125

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Spermatogonial stem cell (SSC) transplantation has been shown to restore fertility in several species and may have application for treating some cases of male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich SSCs from human testis cell suspensions and also remove malignant contamination. We used flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT-4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not expressed on human spermatogonia. A multiparameter sort of MOLT-4-contaminated human testicular cell suspensions was performed to isolate EpCAM + /HLA-ABC -/CD49e -(putative spermatogonia) and EpCAM -/HLA-ABC + /CD49e + (putative MOLT-4) cell fractions. The EpCAM + /HLA-ABC -/CD49e -fraction was enriched for spermatogonial colonizing activity and did not form tumors following human-to-nude mouse xenotransplantation. The EpCAM -/HLA-ABC + / CD49e + fraction produced tumors following xenotransplantation. This approach could be generalized with slight modification to also remove contaminating TF-1a leukemia cells. Thus, FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression.

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Section: Introductionmentioning

confidence: 99%

Eliminating malignant contamination from therapeutic human spermatogonial stem cells

Dovey¹,

Valli²,

Hermann³

et al. 2013

J. Clin. Invest.

125

View full text Add to dashboard Cite

show abstract

“…SSC transplantation has proven effective for regenerating spermatogenesis and fertility in small and large animal models (Brinster and Avarbock, 1994;Ogawa et al, 2000;Shinohara et al, 2001;Nagano et al, 2001;Brinster et al, 2003;Honaramooz et al, 2003;Orwig and Schlatt, 2005;Mikkola et al, 2006;Kim et al, 2008). Clinical translation of this technique is imminent and may provide hope for future fertility in cases where there are no other options to preserve and/or restore fertility, such as prepubertal cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…Although prepubertal boys are not making sperm, their testes contain SSCs that are poised to initiate spermatogenesis at puberty (Ehmcke et al, 2006;Culty, 2009;Wu et al, 2009). In animal models (rodents, pigs, goats and dogs), transplantation of SSCs into the testes of infertile males can lead to restoration of spermatogenesis (Brinster and Avarbock, 1994;Ogawa et al, 2000;Shinohara et al, 2001;Nagano et al, 2001;Brinster et al, 2003;Honaramooz et al, 2003;Orwig and Schlatt, 2005;Mikkola et al, 2006;Kim et al, 2008). Stem cells from all ages, newborn to adult, are competent to produce complete spermatogenesis following transplantation into recipient testes (Shinohara et al, 2001;Ryu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Separating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions

et al. 2011

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background: Chemotherapy and radiation treatments for cancer and other diseases can cause male infertility. There are currently no options to preserve the fertility of prepubertal boys who are not yet making sperm. Cryopreservation of spermatogonial stem cells (SSCs, obtained via testicular biopsy) followed by autologous transplantation back into the testes at a later date may restore fertility in these patients. However, this approach carries an inherent risk of reintroducing cancer.methods: To address this aspect of SSC transplantation safety, prepubertal non-human primate testis cell suspensions were inoculated with MOLT4 T-lymphoblastic leukemia cells and subsequently sorted for cell surface markers CD90 (THY-1) and CD45.results: Cancer cells segregated to the CD902/CD45+ fraction and produced tumors in nude mice. Nearly all sorted DEAD box polypeptide 4-positive (VASA+) spermatogonia segregated to the CD90+/CD452 fraction. In a preliminary experiment, a purity check of the sorted putative stem cell fraction (CD90+/CD452) revealed 0.1% contamination with cancer cells, which was sufficient to produce tumors in nude mice. We hypothesized that the contamination resulted from mis-sorting due to cell clumping and employed singlet discrimination (SD) in four subsequent experiments. Purity checks revealed no cancer cell contamination in the CD90+/CD452 fraction from three of the four SD replicates and these fractions produced no tumors when transplanted into nude mouse testes.conclusions: We conclude that spermatogonia can be separated from contaminating malignant cells by fluorescence-activated cell sorting prior to SSC transplantation and that post-sorting purity checks are required to confirm elimination of malignant cells.

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“…As reported, SSCs from domestic species could colonize and proliferate in host mouse testes after transplantation, but could not give rise to entire spermatogenesis , Izadyar et al 2002, Oatley et al 2002, Kim et al 2006; Table 2), probably due to the phylogenetic disparity between donors and hosts. Later, allogeneic transplantation of SSCs was tested in boars, bulls, goats, sheep, and dogs (Honaramooz et al 2002a, Izadyar et al 2003, Herrid et al 2006, 2009b, Kim et al 2008, and the development of the donor germ cells was observed in those recipients of homogeneous species ( Fig. 2A and Table 2).…”

Section: Transplantation Of Sscs From Domestic Animalsmentioning

confidence: 99%

Spermatogonial stem cells from domestic animals: progress and prospects

Zheng

Zhang

et al. 2014

Reproduction

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Spermatogenesis, an elaborate and male-specific process in adult testes by which a number of spermatozoa are produced constantly for male fertility, relies on spermatogonial stem cells (SSCs). As a sub-population of undifferentiated spermatogonia, SSCs are capable of both self-renewal (to maintain sufficient quantities) and differentiation into mature spermatozoa. SSCs are able to convert to pluripotent stem cells during in vitro culture, thus they could function as substitutes for human embryonic stem cells without ethical issues. In addition, this process does not require exogenous transcription factors necessary to produce induced-pluripotent stem cells from somatic cells. Moreover, combining genetic engineering with germ cell transplantation would greatly facilitate the generation of transgenic animals. Since germ cell transplantation into infertile recipient testes was first established in 1994, in vivo and in vitro study and manipulation of SSCs in rodent testes have been progressing at a staggering rate. By contrast, their counterparts in domestic animals, despite the failure to reach a comparable level, still burgeoned and showed striking advances. This review outlines the recent progressions of characterization, isolation, in vitro propagation, and transplantation of spermatogonia/SSCs from domestic animals, thereby shedding light on future exploration of these cells with high value, as well as contributing to the development of reproductive technology for large animals.Reproduction (2014) 147 R65-R74

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Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog

Cited by 112 publications

References 45 publications

Eliminating malignant contamination from therapeutic human spermatogonial stem cells

Eliminating malignant contamination from therapeutic human spermatogonial stem cells

Separating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions

Spermatogonial stem cells from domestic animals: progress and prospects

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