ArticleReproductive biology and endocrinology : RB&E2015
Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer.
Article in Reproductive biology and endocrinology : RB&E, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Mesenchymal Stem Cells (MSCs) Therapy for Recovery of Fertility: a Systematic Review.Stem cell reviews and reports · 2018Pooled it
- Relationship Between VSELs, MUSE Cells and MSCs in Health and Disease.Stem cell reviews and reports · 2026Review
- Reviewing the Implication of Aldehyde Dehydrogenases in Male Reproduction: Prospects for New Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Dysfunctional, Tissue-Resident, Very Small Embryonic-Like Stem Cells (VSELs) Initiate Cancer and Result in its Progression and Metastasis, Independent of Epithelial-Mesenchymal Transition.Stem cell reviews and reports · 2026Review
- Small adipose-derived mesenchymal stromal cells exhibit longer telomeres and enhanced regenerative potential.Frontiers in bioengineering and biotechnology · 2025Article
- Sertoli cells-only syndrome: current clinical approaches and ongoing research trends.Frontiers in endocrinology · 2025Review
- The Evolutionary Route of in vitro Human Spermatogenesis: What is the Next Destination?Stem cell reviews and reports · 2024Review
- Initiation of Cancer: The Journey From Mutations in Somatic Cells to Epigenetic Changes in Tissue-resident VSELs.Stem cell reviews and reports · 2024Review
- Current Progress in Stem Cell Therapy for Male Infertility.Stem cell reviews and reports · 2023Review
- Autologous Human Mesenchymal Stem Cell-Based Therapy in Infertility: New Strategies and Future Perspectives.Biology · 2023Review
- Long-Term Outcomes in Survivors of Childhood Cancer: A 30-Year Experience From India.JCO global oncology · 2022Article
- Endogenous, tissue-resident stem/progenitor cells in gonads and bone marrow express FSHR and respond to FSH via FSHR-3.Journal of ovarian research · 2021Review
- Review
- Testicular Stem Cells Survive Oncotherapy.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Review
- Testicular Stem Cell Dysfunction Due to Environmental Insults Could Be Responsible for Deteriorating Reproductive Health of Men.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Research Advances in Gametogenesis and Embryogenesis Using Pluripotent Stem Cells.Frontiers in cell and developmental biology · 2021Review
- Busulfan Suppresses Autophagy in Mouse Spermatogonial Progenitor Cells via mTOR of AKT and p53 Signaling Pathways.Stem cell reviews and reports · 2020Article
- Stem cell-based therapies for fertility preservation in males: Current status and future prospects.World journal of stem cells · 2020Review
- Additional Evidence to Establish Existence of Two Stem Cell Populations Including VSELs and SSCs in Adult Mouse Testes.Stem cell reviews and reports · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInfertility is a known side-effect of oncotherapy in cancer survivors, and often compromises the quality of life. The present study was undertaken to detect very small embryonic-like stem cells (VSELs) in testicular biopsies from young adult survivors of childhood cancer who had azoospermia. VSELs have been earlier reported in human and mouse testes. They resist busulphan treatment in mice and potentially restore spermatogenesis when the somatic niche is restored by transplanting Sertoli or mesenchymal cells. VSELs also have the potential to differentiate into sperm in vitro.
methodsThe study had clearance from Institutional review board (IRB). Seven azoospermic survivors of childhood cancer were included in the study after obtaining their informed consent. Semen analysis was done to confirm azoospermia prior to inclusion in the study. Testicular biopsies were performed at the Uro-oncology Unit of the hospital and then used for various studies to detect VSELs.
resultsHematoxylin and Eosin stained tubular sections confirmed azoospermia and smears revealed the presence of very small, spherical VSELs with high nucleo-cytoplasmic ratio, in addition to the Sertoli cells. Immuno-localization studies on testicular smears showed that the VSELs were CD133+/CD45-/LIN-, expressed nuclear OCT-4, STELLA and cell surface SSEA-4. Pluripotent transcripts Oct-4A, Nanog and Sox-2 were detected in azoospermic samples whereas marked reduction was observed in germ cell markers Oct-4 and Boule.
conclusionsThe present study demonstrates the presence of pluripotent VSELs in the testicular biopsy of azoospermic adult survivors of childhood cancer. It is likely that these persisting VSELs can restore spermatogenesis as demonstrated in mice studies. Therefore, pilot studies need to be undertaken using autologous mesenchymal cells with a hope to restore testicular function and fertility in cancer survivors. The results of this study assume a great significance in the current era, where cryopreservation of testicular tissue in young pre-pubertal boys for restoring spermatogenesis in adulthood is still in experimental stages.
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