In search of an improved injection technique for the clinical application of spermatogonial stem cell transplantation

Faes, Katrien; Lahoutte, Tony; Hoorens, Anne; Tournaye, Herman; Goossens, Ellen

doi:10.1016/j.rbmo.2016.12.007

Cited by 20 publications

(11 citation statements)

References 26 publications

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“…Although the cells were injected into the rete testis and on ultrasound appeared to enter the tubules, some transplanted cells must have inadvertently leaked into the interstitial space, as shown previously with rete injection in human tissue (Faes et al, 2017). In our rat studies, de novo tubule formation was enhanced when interstitial injection was employed as opposed to the attempted rete testis injection (Zhang et al, 2009).…”

Section: Discussionsupporting

confidence: 67%

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Donor spermatogenesis in de novo formed seminiferous tubules from transplanted testicular cells in rhesus monkey testis

et al. 2018

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Can transplanted primate testicular cells form seminiferous tubules de novo, supporting complete spermatogenesis? SUMMARY ANSWER: Cryopreserved testicular cells from a prepubertal monkey can reorganize in an adult monkey recipient testis forming de novo seminiferous tubular cords supporting complete spermatogenesis.WHAT IS KNOWN ALREADY: De novo morphogenesis of testicular tissue using aggregated cells from non-primate species grafted either subcutaneously or in the testis can support spermatogenesis. STUDY DESIGN, SIZE, DURATION: Two postpubertal rhesus monkeys (Macaca mulatta) were given testicular irradiation. One monkey was given GnRH-antagonist treatment from 8 to 16 weeks after irradiation, while the other received sham injections. At 16 weeks, cryopreserved testicular cells from two different prepubertal monkeys [43 × 10 6 viable (Trypan-blue excluding) cells in 260 μl, and 80 × 10 6 viable cells in 400 μl] were transplanted via ultrasound-guided injections to one of the rete testis in each recipient, and immune suppression was given. The contralateral testis was sham transplanted. Testes were analyzed 9 months after transplantation.PARTICIPANTS/MATERIALS, SETTING, METHODS: Spermatogenic recovery was assessed by testicular volume, weight, histology and immunofluorescence. Microsatellite genotyping of regions of testicular sections obtained by LCM determined whether the cells were derived from the host or transplanted cells. MAIN RESULTS AND THE ROLE OF CHANCE:Transplanted testis of the GnRH-antagonist-treated recipient, but not the shamtreated recipient, contained numerous irregularly shaped seminiferous tubular cords, 89% of which had differentiating germ cells, including sperm in a few of them. The percentages of donor genotype in different regions of this testis were as follows: normal tubule, 0%; inflammatory, 0%; abnormal tubule region, 67%; whole interior of abnormal tubules, >99%; adluminal region of the abnormal tubules, 92%. Thus, these abnormal tubules, including the enclosed germ cells, were derived de novo from the donor testicular cells.LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION:The de novo tubules were observed in only one out of the two monkeys transplanted with prepubertal donor testicular cells.

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Section: Discussionsupporting

confidence: 67%

“…Another possible factor is that the hormone suppression given to M1 just prior to transplantation stimulated de novo tubule formation. A third reason for different results between M1 and M2 may be the variation in interstitial leakage during rete testis injection (Faes et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Donor spermatogenesis in de novo formed seminiferous tubules from transplanted testicular cells in rhesus monkey testis

et al. 2018

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“…Studies have confirmed that SSC transplantation does not increase the risk of tumor formation or reduce longevity in mice and that the genome of offspring is unchanged[ 82 , 83 ]. Future studies should consider strategies to achieve further improvements in the efficiency of SSC transplantation and reductions in SSC loss[ 84 ]. Increasing research results support the potential use of SSCs to restore fertility in clinical applications[ 85 ].…”

Section: Spermatogonial Stem Cells and Their Nichementioning

confidence: 99%

Stem cell-based therapies for fertility preservation in males: Current status and future prospects

Liu¹,

Xie²,

Deng³

et al. 2020

WJSC

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With the decline in male fertility in recent years, strategies for male fertility preservation have received increasing attention. In this study, by reviewing current treatments and recent publications, we describe research progress in and the future directions of stem cell-based therapies for male fertility preservation, focusing on the use of spermatogonial stem cells (SSCs), SSC niches, SSC-based testicular organoids, other stem cell types such as mesenchymal stem cells, and stem cell-derived extracellular vesicles. In conclusion, a more comprehensive understanding of the germ cell microenvironment, stem cell-derived extracellular vesicles, and testicular organoids will play an important role in achieving male fertility preservation.

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“…Using cadaver testes, ultrasound-guided injection in the rete testis has been determined as the best technique for cell transplantation in larger testes. 84,85 So far, only one report has described autotransplantation of cryopreserved human TCSs in patients cured of non-Hodgkin's lymphoma, but no follow-up was published. 86 An important clinical concern is the risk of cancer-cell contamination of the TCSs to be transplanted, since transplantation of only 20 leukemic cells in rats has resulted in cancer relapse.…”

Section: Transplantation Of Isolated Sscsmentioning

confidence: 99%

<p>Role of stem cells in fertility preservation: current insights</p>

Vermeulen¹,

Giudice²,

Vento³

et al. 2019

SCCAA

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While improvements made in the field of cancer therapy allow high survival rates, gonadotoxicity of chemo- and radiotherapy can lead to infertility in male and female pre- and postpubertal patients. Clinical options to preserve fertility before starting gonadotoxic therapies by cryopreserving sperm or oocytes for future use with assisted reproductive technology (ART) are now applied worldwide. Cryopreservation of pre- and postpubertal ovarian tissue containing primordial follicles, though still considered experimental, has already led to the birth of healthy babies after autotransplantation and is performed in an increasing number of centers. For prepubertal boys who do not produce gametes ready for fertilization, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells may be proposed as an experimental strategy with the aim of restoring fertility. Based on achievements in nonhuman primates, autotransplantation of ITT or testicular cell suspensions appears promising to restore fertility of young cancer survivors. So far, whether in two- or three-dimensional culture systems, in vitro maturation of immature male and female gonadal cells or tissue has not demonstrated a capacity to produce safe gametes for ART. Recently, primordial germ cells have been generated from embryonic and induced pluripotent stem cells, but further investigations regarding efficiency and safety are needed. Transplantation of mesenchymal stem cells to improve the vascularization of gonadal tissue grafts, increase the colonization of transplanted cells, and restore the damaged somatic compartment could overcome the current limitations encountered with transplantation.

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In search of an improved injection technique for the clinical application of spermatogonial stem cell transplantation

Cited by 20 publications

References 26 publications

Donor spermatogenesis in de novo formed seminiferous tubules from transplanted testicular cells in rhesus monkey testis

Donor spermatogenesis in de novo formed seminiferous tubules from transplanted testicular cells in rhesus monkey testis

Stem cell-based therapies for fertility preservation in males: Current status and future prospects

<p>Role of stem cells in fertility preservation: current insights</p>

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