20
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Co-transplantation of mesenchymal stem cells improves spermatogonial stem cell transplantation efficiency in mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Spermatogonial stem cell transplantation (SSCT) could become a fertility restoration tool for childhood cancer survivors. 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. Co-transplantation of mesenchymal stem cells (MSCs) might increase colonization efficiency of SSCs by restoring the SSC niche after gonadotoxic treatment.

          Methods

          A mouse model for long-term infertility was developed and used to transplant SSCs (SSCT, n = 10), MSCs (MSCT, n = 10), a combination of SSCs and MSCs (MS-SSCT, n = 10), or a combination of SSCs and TGFß1-treated MSCs (MSi-SSCT, n = 10).

          Results

          The best model for transplantation was obtained after intraperitoneal injection of busulfan (40 mg/kg body weight) at 4 weeks followed by CdCl 2 (2 mg/kg body weight) at 8 weeks of age and transplantation at 11 weeks of age. Three months after transplantation, spermatogenesis resumed with a significantly better tubular fertility index (TFI) in all transplanted groups compared to non-transplanted controls ( P < 0.001). TFI after MSi-SSCT (83.3 ± 19.5%) was significantly higher compared to MS-SSCT (71.5 ± 21.7%, P = 0.036) but did not differ statistically compared to SSCT (78.2 ± 12.5%). In contrast, TFI after MSCT (50.2 ± 22.5%) was significantly lower compared to SSCT ( P < 0.001). Interestingly, donor-derived TFI was found to be significantly improved after MSi-SSCT (18.8 ± 8.0%) compared to SSCT (1.9 ± 1.1%; P < 0.001), MSCT (0.0 ± 0.0%; P < 0.001), and MS-SSCT (3.4 ± 1.9%; P < 0.001). While analyses showed that both native and TGFß1-treated MSCs maintained characteristics of MSCs, the latter showed less migratory characteristics and was not detected in other organs.

          Conclusion

          Co-transplanting SSCs and TGFß1-treated MSCs significantly improves the recovery of endogenous SSCs and increases the homing efficiency of transplanted SSCs. This procedure could become an efficient method to treat infertility in a clinical setup, once the safety of the technique has been proven.

          Electronic supplementary material

          The online version of this article (10.1186/s13287-018-1065-0) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives.

          Mesenchymal stem cells (MSCs) are one of a few stem cell types to be applied in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair. In addition to their multipotent differentiation potential, a strong paracrine capacity has been proposed as the principal mechanism that contributes to tissue repair. Apart from cytokine/chemokine secretion, MSCs also display a strong capacity for mitochondrial transfer and microvesicle (exosomes) secretion in response to injury with subsequent promotion of tissue regeneration. These unique properties of MSCs make them an invaluable cell type to repair damaged tissues/organs. Although MSCs offer great promise in the treatment of degenerative diseases and inflammatory disorders, there are still many challenges to overcome prior to their widespread clinical application. Particularly, their in-depth paracrine mechanisms remain a matter for debate and exploration. This review will highlight the discovery of the paracrine mechanism of MSCs, regulation of the paracrine biology of MSCs, important paracrine factors of MSCs in modulation of tissue repair, exosome and mitochondrial transfer for tissue repair, and the future perspective for MSC-based therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys.

            What clinical practices, patient management strategies and experimental methods are currently being used to preserve and restore the fertility of prepubertal boys and adolescent males?
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults.

              Preservation of gonadal function is an important priority for the long-term health of cancer survivors of both sexes and all ages at treatment. Loss of opportunity for fertility is a prime concern in both male and female cancer survivors, but endocrine effects of gonadal damage are likewise central to long-term health and wellbeing. Some fertility preservation techniques, such as semen and embryo cryopreservation, are established and successful in adults, and development of oocyte vitrification has greatly improved the potential to cryopreserve unfertilised oocytes. Despite being recommended for all pubertal male patients, sperm banking is not universally practised in paediatric oncology centres, and very few adolescent-friendly facilities exist. All approaches to fertility preservation have specific challenges in children and teenagers, including ethical, practical, and scientific issues. For young women, cryopreservation of ovarian cortical tissue with later replacement has resulted in at least 40 livebirths, but is still regarded as experimental in most countries. For prepubertal boys, testicular biopsy cryopreservation is offered in some centres, but how that tissue might be used in the future is unclear, and so far no evidence suggests that fertility can be restored. For both sexes, these approaches involve an invasive procedure and have an uncertain risk of tissue contamination in haematological and other malignancies. Decision making for all these approaches needs assessment of the individual's risk of fertility loss, and is made at a time of emotional distress. Development of this specialty needs better provision of information for patients and their medical teams, and improvements in service provision, to match technical and scientific advances.
                Bookmark

                Author and article information

                Contributors
                prashant.kadam@vub.be
                elissavet.ntemou@vub.be
                yoni.baert@vub.be
                sven.van.laere@vub.be
                dorien.van.saen@vub.be
                ellen.goossens@vub.be
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                21 November 2018
                21 November 2018
                2018
                : 9
                : 317
                Affiliations
                [1 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Biology of the Testis (BITE) Laboratory, Department of Reproduction, Genetics and Regenerative Medicine, , Vrije Universiteit Brussel (VUB), ; Laarbeeklaan 103, 1090 Brussels, Belgium
                [2 ]ISNI 0000 0001 2290 8069, GRID grid.8767.e, Biostatistics and Medical Informatics (BISI) Research Group, Department of Public Health, , Vrije Universiteit Brussel (VUB), ; Laarbeeklaan 103, 1090 Brussels, Belgium
                Author information
                http://orcid.org/0000-0003-3972-0809
                Article
                1065
                10.1186/s13287-018-1065-0
                6249754
                30463610
                e7f861f0-5e41-47f2-b3a5-86e54811f9d2
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 September 2018
                : 19 October 2018
                : 31 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001503, Indian Council of Agricultural Research;
                Award ID: International Fellowship
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100011264, FP7 People: Marie-Curie Actions;
                Award ID: EU-FP7-PEOPLE-2013-ITN 603568
                Award ID: EU-FP7-PEOPLE-2013-ITN 603568
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100003130, Fonds Wetenschappelijk Onderzoek;
                Funded by: FundRef http://dx.doi.org/10.13039/501100004418, Vrije Universiteit Brussel;
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Molecular medicine
                fertility restoration,infertility,mesenchymal stem cells,spermatogonial stem cells,transplantation

                Comments

                Comment on this article