Very small embryonic-like stem cells (VSELs) detected in azoospermic testicular biopsies of adult survivors of childhood cancer

Reproductive Biology and Endocrinology

Research

Purna Kurkure¹  Vandana Dhamankar¹  Maya Prasad¹  Ganesh Bakshi² 

[1] ACT Clinic, Department of Pediatric Oncology, Dr E Borges Road, Parel, 400012, Mumbai, India;Division of Uro-oncology, Tata Memorial Hospital, Dr E Borges Road, Parel, 400012, Mumbai, India;

关键词: Cancer;    Oncotherapy;    Azoospermia;    VSELs;    Spermatogenesis;    Stem cells;   

DOI  :  10.1186/s12958-015-0121-1

 received in 2015-06-04, accepted in 2015-11-02,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Kurkure et al. 2015