Autologous spermatogonial stem cell transplantation in man: current obstacles for a future clinical application

Geens, Mieke; Goossens, Ellen; Block, Gert De; Liang, Ning; Saen, Dorien Van; Tournaye, Herman

doi:10.1093/humupd/dmm047

Cited by 57 publications

(32 citation statements)

References 75 publications

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“…Not surprisingly, fertility preservation is an important issue in regard to the long-term quality of life. Cryopreservation of small fragments of testicular tissue is an experimental strategy for fertility preservation in cases where cryopreservation of sperm is not applicable (see Geens et al, 2008;Schlatt et al, 2009 for review).…”

Section: Introductionmentioning

confidence: 99%

What is the best cryopreservation protocol for human testicular tissue banking?

et al. 2013

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study question: Is there a better alternative to the conventional cryopreservation protocols for human testicular tissue banking? summary answer: Uncontrolled slow freezing (USF) using 1.5 M dimethylsulphoxide (DMSO) and 0.15 M sucrose as cryoprotectants appears to be a user-friendly and efficient method for the cryopreservation of human testicular tissue.what is known already: Currently, time-consuming controlled slow freezing (CSF) protocols that need expensive equipment are commonly used for human testicular tissue banking. USF and vitrification are cryopreservation techniques that were successfully applied in several animal models but need further exploration with human tissue. study design, size, duration: Fragments (n ¼ 160) of testicular tissue from 14 patients undergoing vasectomy reversal were assigned to a fresh control group or one of the following cryopreservation procedures: CSF using DMSO at a concentration of 0.7 or 1.5 M in the presence (+S) or absence of sucrose (2S), USF using either 0.7 or 1.5 M DMSO combined with sucrose, solid-surface vitrification (SSV) or direct cover vitrification (DCV). materials, setting, methods: Light microscopic evaluations were performed to study apoptosis, germ cell proliferation ability, spermatogonial survival, coherence of the seminiferous epithelium and integrity of the interstitial compartment after cryopreservation. Ultrastructural alterations were studied by scoring cryodamage to four relevant testicular cell types.main results and the role of chance: The USF 1.5 M DMSO + S protocol proved not solely to prevent cell death and to preserve seminiferous epithelial coherence, interstitial compartment integrity, SG and their potential to divide but also protected the testicular cell ultrastructure. A significant reduction in the number of SG per tubule from 21.4 + 5.6 in control tissue to 4.9 + 2.1, 8.2 + 5.4, 11.6 + 5.1, 8.8 + 3.9, 12.6 + 4.4 and 11.7 + 5.7 was observed after cryopreservation combined with at least one other form of cryoinjury when using CSF 0.7 M DMSO 2S, CSF 0.7 M DMSO + S, CSF 1.5 M DMSO + S, USF 0.7 M DMSO + S, SSV and direct cover vitrification (DCV), respectively (P , 0.001).limitations, reasons for caution: Supplementary research is required to investigate the effect on tissue functionality and to confirm this study's findings using prepubertal tissue.wider implications of the findings: An optimal cryopreservation protocol enhances the chances for successful fertility restoration. USF, being an easy and cost-effective alternative to CSF, would be preferable for laboratories in developing countries or whenever tissue is to be procured from a diseased child at a site distant from the banking facility.

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Section: Introductionmentioning

confidence: 99%

What is the best cryopreservation protocol for human testicular tissue banking?

et al. 2013

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“…Furthermore, the regenerative potential of SSCs has been exploited in a transplantation paradigm to restore spermatogenesis in infertile animal models [rodents (Ogawa et al ., 2000; Nagano et al ., 2001; Brinster et al ., 2003; Ryu et al ., 2003), goats (Honaramooz et al ., 2003) and dogs (Kim et al ., 2008)]. This stem cell therapy may one day have application for treating some cases of human male infertility (reviewed in Orwig and Schlatt, 2005; Brinster, 2007; Geens et al ., 2008). Elucidating fundamental characteristics of the SSC pool in a non-human primate model may facilitate translation of SSC transplantation to the clinic.…”

Section: Introductionmentioning

confidence: 99%

Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques

et al. 2009

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BACKGROUNDThe spermatogonial stem cell (SSC) pool in the testes of non-human primates is poorly defined.METHODSTo begin characterizing SSCs in rhesus macaque testes, we employed fluorescence-activated cell sorting (FACS), a xenotransplant bioassay and immunohistochemical methods and correlated our findings with classical descriptions of germ cell nuclear morphology (i.e. Adark and Apale spermatogonia).RESULTSFACS analysis identified a THY-1+ fraction of rhesus testis cells that was enriched for consensus SSC markers (i.e. PLZF, GFRα1) and exhibited enhanced colonizing activity upon transplantation to nude mouse testes. We observed a substantial conservation of spermatogonial markers from mice to monkeys [PLZF, GFRα1, Neurogenin 3 (NGN3), cKIT]. Assuming that molecular characteristics correlate with function, the pool of putative SSCs (THY-1+, PLZF+, GFRα1+, NGN3+/−, cKIT−) comprises most Adark and Apale and is considerably larger in primates than in rodents. It is noteworthy that the majority of Adark and Apale share a common molecular phenotype, considering their distinct functional classifications as reserve and renewing stem cells, respectively. NGN3 is absent from Adark, but is expressed by some Apale and may mark the transition from undifferentiated (cKIT−) to differentiating (cKIT+) spermatogonia. Finally, the pool of transit-amplifying progenitor spermatogonia (PLZF+, GFRα1+, NGN3+, cKIT+/−) is smaller in primates than in rodents.CONCLUSIONSThese results provide an in-depth analysis of molecular characteristics of primate spermatogonia, including SSCs, and lay a foundation for future studies investigating the kinetics of spermatogonial renewal, clonal expansion and differentiation during primate spermatogenesis.

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“…To safeguard their ability to father their genetically own children, cryopreservation of testicular tissue containing SSCs followed by transplantation is a potential fertility preservation strategy (4). Undoubtedly, cryopreservation of testicular tissue is a challenging task.…”

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confidence: 99%