The fate of sscs is directed by their surrounding microenvironment niche consisting of supporting cells. Type b cells, which divide to give rise to primary. Pdf spermatogonial stem cell transplantation laura. Transplantation of spermatogonial stem cells springerlink. We are entering an exciting epoch in livestock biotechnology during which the fundamental approaches such as transgenesis, spermatozoa cryopreservation and artificial insemination will be enhanced based on the modern understanding of the biology of spermatogonial stem cells sscs combined with the outstanding recent advances in genomic editing technologies and in vitro cell culture systems. Genetic reconstruction of mouse spermatogonial stem cell. Spermatogonial stem cells sscs are the foundation for spermatogenesis and, thus, preservation of a species. The testes of this stage contain an enriched population of spermatogonial stem cells and have a higher frequency of retrovirus infection than those from mature testes 7, 22. After centurylong research, proofofprinciple culture systems have been introduced to support the. Development of spermatogonial stem cell transplantation method. Clonal origin of germ cell colonies after spermatogonial. Nov 02, 2012 spermatogonial stem cells sscs maintain spermatogenesis throughout a mans life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. Although several cytokines coordinate to drive ssc selfrenewal, little is known. Earlier studies have shown that the transplantation of sscs restores fertility to infertile recipients.
Spermatogonial stem cells sscs are the most primitive spermatogonia in the testis and have an essential role to maintain highly. This discovery not only provided a clue to understand ssc selfrenewing mechanisms but also made it. Introduction spermatogonial stem cells sdcs are part of a subset of male germ cells which are called undifferentiated spermatogonia 1. Sscs constantly undergo selfrenewal division on the. Spermatogonial stem cell transplantation ssct could become a fertility restoration tool for. Spermatogonial stem cell transplantation into rhesus testes. Spermatogonial stem cell ssc banking followed by autologous transplantation has been proposed as a fertility preservation strategy. Genetic and epigenetic changes after spermatogonial stem cell. The source of the donor cells for transplantation into recipient testes can be a testicular singlecell suspension, in vitrocultured cells enriched for spermatogonial stem cells, or cells. In fact, radford and colleagues26,27 reported a clinical trial in 1999 in which testicular cell suspensions were cryopreserved for 12 patients with hodgkin disease. Can mesenchymal stem cells improve spermatogonial stem cell. Spermatogonial stem cells, infertility and testicular cancer.
The scheme capitalizes on the capacity of spermatogonial stem cells to regenerate sperm production after isolation from donor testicular tissue and transfer into the testes of a recipient male that lacks endogenous germline, thereby allowing the surrogate male to produce offspring with the donor haplotype via natural mating. This is the alternative ssc outcome to selfrenewal. Smith zz from the department of urology, molecular and integrated physiology, and obstetrics and gynecology, university of michigan, ann arbor, michigan. However, the low efficiency of ssct is a significant concern. However, in fish, the lack of ssc molecular markers represents a great limitation to identifypurify these cells, rendering it difficult to apply several. Spermatogonial stem cells sscs are crucial for maintaining spermatogenesis throughout life, and understanding how these cells function has important implications for understanding male infertility. Spermatogonial stem cell transplantation request pdf. Cryopreservation of mouse spermatogonial stem cells in. In 2000, glial cell linederived neurotrophic factor was identified as a ssc selfrenewal factor.
As these boys do not yet produce sperm cells, they cannot bene. Spermatogonial stem cell transplantation into rhesus. Continual function of this process is a requirement for sustained male fertility. In association with in vitro culture and transplantation, isolation of spermatogonial stem cells sscs is an excellent approach for investigating spermatogonial physiology in vertebrates. An overview of spermatogonial stem cells physiology, niche. Spermatogonial stem cell transplantation and male infertility. Whereas rare a single spermatogonia comprise the rodent ssc pool, primate spermatogenesis arises from more abundant a dark and a pale spermatogonia, and the identity of the stem cell is subject to debate. Spermatogonial stem cells biology of reproduction oxford. Germline, stem cells, wnt signaling, mouse accepted 6 march 2011. Spermatogonial stem cells sscs undergo selfrenewal division and support spermatogenesis. Pdf isolation, cryopreservation, and transplantation of.
Phenotypic characterization and in vitro propagation and. In vivo genetic manipulation of spermatogonial stem cells. Characterization, cryopreservation, and ablation of. Spermatogonial stem cell niche and spermatogonial stem cell transplantation in zebrafish. Spermatogonial stem cells as a therapeutic alternative for. Manipulation of spermatogonial stem cells in livestock species ncbi. Spermatogenesis originates from spermatogonial stem cells sscs.
Spermatogonial stem cells sscs provide the foundation for spermatogenesis. Pdf advances in spermatogonial stem cell transplantation. Wnt5a is a cellextrinsic factor that supports self renewal. However, it is generally impossible to rescue tissue dysfunction caused by defective microenvironment. These cells are reserve spermatogonial stem cells which do not usually undergo active mitosis. The spermatogonial stem cells sscs are responsible for the transmission of genetic information from an individual to the next generation. Spermatogonial stem cells sscs sustain spermatogenesis that occurs continuously in the adult testis. Transplantation of spermatogonial stem cells from fertile, transgenic donor mice to the testes of infertile recipients provides a unique system to study the biology of spermatogonial stem cells.
At the foundation of spermatogenesis are the actions of spermatogonial stem cells sscs, and a remarkable feature of these cells is the capacity to regenerate. However, only 510% of the transplanted cells colonize recipient testes. We are entering an exciting epoch in livestock biotechnology during which the fundamental approaches such as transgenesis, spermatozoa cryopreservation and artificial insemination will be enhanced based on the modern understanding of the biology of spermatogonial stem cells sscs combined with the outstanding recent advances in genomic editing technologies and in vitro cell. Spermatogonial stem cell transplantation ssct could become a fertility restoration tool for childhood cancer survivors. Transplantation of autologous or allogeneic spermatogonial stem cells can restore fertility after chemotherapy in rhesus macaques, paving the way for clinical translation.
Jul 27, 2005 spermatogonial stem cells sscs are responsible for the continual production of spermatozoa throughout adult life. Autologous transplantation of spermatogonial stem cells. Cells free fulltext spermatogonial stem cells for in. May 26, 2015 spermatogonial stem cells sscs are the germ stem cells of the seminiferous epithelium in the testis.
Ssct could be improved by cotransplanting transforming growth factor beta 1 tgf. The nature and dynamics of spermatogonial stem cells. Stem cell transplantation is widely used to rescue defects in stem cell derived cells. Interactions between sscs and the surrounding cells in the seminiferous tubules regulate the biological activity of these cells. Transplantation experiments involving the testis have been of two types, those in which the testis was. Spermatogonial stem cells sscs are at the foundation of mammalian spermatogenesis.
The early history of organ transplantation dates back to the second century before christ 1. Identifying genes important for spermatogonial stem cell. Finally, we will discuss some advances on ssc phenotypic characterization, cell culture and future perspectives. Spermatogonial stem cells sscs are the germ stem cells of the seminiferous epithelium in the testis. After transplantation, the donor spermatogonial stem cells repopulate the seminiferous epithelium of the recipient mice. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. After transplantation to recipient testes, sscs can colonize and initiate donorderived.
Testicular tissue cryopreservation is the preferred method to. Mice spermatogonial stem cells transplantation induces. Two cryopreservation strategies for spermatogonial stem cells sscs were compared in a mouse model. Transplanted spermatogonial stem cells sscs produce germ cell. Mice spermatogonial stem cells transplantation induces macrophage migration into the seminiferous epithelium and lipid body formation. Testicular tissue samples from azoospermic patients were obtained and then these were freezethawed. Despite their biological importance, these cells have not been wellcharacterized due to their small population size and lack of specific markers. Staining of the cells was verified under a fluorescent microscope, and the cells. Genetic and epigenetic changes after spermatogonial stem. These are the spermatogonial stem cells that undergo active mitosis. Tournaye1,2 1biology of the testis bite, department for embryology and genetics, vrije universiteit brussel vub, laarbeeklaan 103, brussels 1090. Spermatogonial transplantation and germline stem cells gscs spermatogonial stem cells sscs provide the foundation for spermatogenesis. Pdf spermatogonial stem cell niche and spermatogonial. Interestingly, also rat spermatogonial stem cells are able to repopulate the mouse testis and produce normal rat spermatogenesis in the mouse 46, 47.
Stem cell transplantation is widely used to rescue defects in stem cellderived cells. Spermatogonial stem cells sscs are the only adult stem cells capable of passing genes onto the next generation. Manipulation of spermatogonial stem cells in livestock. Spermatogonial stem cells sscs can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous. Recent advances for spermatogonial stem cell transplantation in. The scheme capitalizes on the capacity of spermatogonial stem cells to regenerate sperm production after isolation from donor testicular tissue and transfer into the testes of a recipient male that lacks. Spermatogonial stem cells are the precursors to spermatozoa, which are produced through a series of differentiation steps. Jul 01, 2006 retroviral infection of spermatogonial stem cells.
Through mechanisms not fully understood they can derive pluripotent stem cells. Fast facts about stem cell transplantation since blood and marrow are both good sources of stem cells for transplantation, the term stem cell transplantation has replaced bone marrow transplantation as the general term for this procedure. Sscs survive within microenvironments, termed niches, which provide extrinsic stimuli that drive stem cell. We used the technique of spermatogonial transplantation in two infertile mouse strains, steel sl and dominant white spotting w, to determine if stem cells from an infertile male were capable. Recently, various populations of cells harbouring stem cell like properties have been identified in rodent seminiferous tubules, but deciphering how these cells. Genetic and epigenetic changes after spermatogonial stem cell culture and transplantation. Assisted reproductive techniques involving isolation, culture, and transplantation of spermatogonial stem cells sscs have the potential to create transgenic livestock. In vitro transplantation of spermatogonial stem cells. Sscs are the founding adult germ stem cells of the sperm producing process spermatogenesis. Highresolution light microscopy and ultrastructural studies volume 17 issue 6 felipe f. Spermatogonial stem cell niche like other stem cells, sscs can selfrenew to replenish the stem cell population or differentiate. In this example, cells are isolated from a lac z donor mouse testis and digested to produce a single cell. However, since in mice, the colonization efficiency of transplanted spermatogonial stem cells sscs is only 12%, the efficiency of the procedure needs to be improved before clinical implementation is possible.
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. But before this technique can be applied in the clinic, some important issues have to be resolved. These results indicate that wnt5a is a cellextrinsic factor that supports ssc selfrenewal through cateninindependent mechanisms. Culture and transplantation of spermatogonial stem cells. Because of stem cell rarity, studying their selfrenewal is greatly facilitated by in vitro culture of enriched biologically active cell populations. Spermatogonial stem cell transplantation into recipient testes fan 40 mgkg. Pdf culture and transplantation of spermatogonial stem cells. Evaluated outcomes were number of viable cells after thawing, number and length of donorderived colonies after spermatogonial stem cell transplantation ssct, number of litters, litter size. At the foundation of spermatogenesis are the spermatogonial stem cells sscs, capable of both selfrenewal and differentiation. Transplantation of male germ line stem cells restores. Factors involved in the regulation of sscs are beginning to be defined by animal models and the culture of sscs in defined media. Instead, they continue dividing into other spermatogonia or remain dormant to maintain a reserve of spermatogonia. In this study, we analyzed the impact of cell cycle on spermatogonial transplantation. Finally, we will discuss some advances on ssc phenotypic characterization, cell.
The functional analysis of sscs is a retrospective assay of spermatogenic function. Essential role of plzf in maintenance of spermatogonial. In this study, we report that autologous spermatogonial stem cell ssc transplantation. Spermatogonial stem cell transplantation ssct is a promising therapy in restoring the fertility of childhood cancer survivors. To summarise the current state of research into spermatogonial stem cell ssc therapies with a focus on future directions, as sscs show promise as a source for. Autologous transplantation of adult mice spermatogonial. Development of the spermatogonial transplantation technique in 1994 provided the first functional assay to characterize sscs. Sscs also have the potential to provide important knowledge about stem cells in general and to offer critical in vitro and in vivo applications in assisted reproductive technologies. Co transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice prashant kadam1, elissavet ntemou1, yoni baert1, sven van laere2, dorien van saen1 and ellen goossens1 abstract background. Pdf the use of spermatogonial stem cells in cancerinduced. In fact, radford and colleagues26,27 reported a clinical trial in 1999 in which testicular cell. Ssc culture, transplantation and plasticity ssc in infertility ssc in testicular germ cell tumours conclusions. However, most of the previously described experiments have depended on transplantation using sexually immature animals, and the effectiveness of spermatogonial. In this experimental research, the right testes from adult mice n25 were collected, then sertoli and spermatogonial cells.
To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich sscs from. Spermatogonial stem cell transplantation and testicular. Spermatogonial stem cells sscs migrate to the niche upon introduction into the seminiferous tubules of the testis of infertile animals. Experimental tools used to study spermatogonial stem cells sscs will be described, along with research using these tools to enhance our understanding of stem cell biology and spermatogenesis. In this manner, sscs are assayed through spermatogonial transplantation whereby testis cells are. The source of the donor cells for transplantation into recipient testes can be a testicular single cell suspension, in vitrocultured cells enriched for spermatogonial stem cells, or cells. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through selfrenewal. Spermatogonial stem cells sscs, the most primitive type of spermatogonia, are found on the basement membrane of seminiferous tubules and characterized by their ability to both selfrenew and differentiate. Spermatogonial stem cell selfrenewal and development. Reviewandrology spermatogonial stem cell preservation and transplantation. Can mesenchymal stem cells improve spermatogonial stem. Recently, various populations of cells harbouring stem celllike properties have been identified in rodent seminiferous tubules, but deciphering how these cells might fuel spermatogenesis has been. The use of spermatogonial stem cells in cancerinduced infertility.
The current study has important implications for the future use of gs cells as an in vitro model for spermatogonial stem cell biology or as a source of embryonic stem. Spermatogonial stem cell isolation, storage, and transplantation. In this study, we report that autologous spermatogonial stem cell ssc transplantation rescues congenital male infertility caused by cldn11 deficiency. If the spermatogonial stem cell ssc niche is destroyed by the anticancer treatment. For the donor cells, we collected testes from 5 to 10dayold b6 pups. Germline transmission of donor haplotype following spermatogonial transplantation. Identifying genes important for spermatogonial stem cell self. Tournaye1,2 1biology of the testis bite, department for. Spermatogonial stem cell preservation and transplantation. Development of the spermatogonial stem cell transplantation technique a decade ago has enabled research on spermatogonial stem cells to shift from morphological cell kinetic, mostly in vivo studies to the development of purification protocols, of better culture systems, and to the detection of molecular characteristics of these cells. Spermatogenesis induction of spermatogonial stem cells using nanofibrous polyl. May 01, 2016 spermatogonial stem cells sscs have the unique ability to undergo selfrenewal division and maintain spermatogenesis for the life span of male animals.
Spermatogonial stem cell isolation, andrology lab corner storage, and transplantation herkanwal khaira, derek mclean, dana a. A spermatogonial stem cell ssc, also known as a type a spermatogonium, is a spermatogonium that does not differentiate into a spermatocyte, a precursor of sperm cells. Does cotransplantation of mesenchymal and spermatogonial. Pdf spermatogonial stem cell transplantation was first reported by ralph brinsters laboratory in 1994. The spermatogonial transplantation technique was developed by dr. Mar 27, 2019 in this study, we examine the progression of spermatogenesis after transplantation of spermatogonial stem cells under conditions of testicular tissue culture. Transplanted spermatogonial stem cells sscs produce germ cell colonies after microinjection into the.
Spermatogonial stem cells sscs can produce numerous male gametes after transplantation into recipient testes, presenting a valuable approach for gene therapy and continuous production of gene. Correction of a genetic disease by crisprcas9mediated gene. Spermatogonial stem cell regulation and spermatogenesis. The abbreviation bmt is now used to represent blood and marrow transplantation. Sscs belong to the male germline and can be expanded in vitro in several species. Manipulation of spermatogonial stem cells in livestock species. Nagano m, brinster r 1998 spermatogonial transplantation and reconstitution of donor cell spermatogenesis in recipient males. Cotransplantation of mesenchymal stem cells improves. Inamannercomparable to hematopoietic stem cell transplantation, sscs colonize the niche of recipient testes and reinitiate spermatogenesis following microinjection into the seminiferous tubules. But before this technique can be applied in the clinic.