Spermatogonial stem cell transplantation and male infertility: Current status and future directions

Peer review under responsibility of Arab Association of Urology.

Abstract

Objective: 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 preserving or initiating fertility in otherwise infertile men.

Materials and methods: We performed a search for publications addressing spermatogonial stem cell transplantation in the treatment of male infertility. The search engines PubMed and Google Scholar were used from 1990 to 2017. Search terms were relevant for spermatogonial stem cell therapies. Titles of publications were screened for relevance; abstracts were read, if related and full papers were reviewed for directly pertinent original research.

Results: In all, 58 papers were found to be relevant to this review, and were included in appropriate subheadings. This review discusses the various techniques that SSCs are being investigated to treat forms of male infertility.

Conclusions: Evidence does not yet support clinical application of SSCs in humans. However, significant progress in the in vitro and in vivo development of SSCs, including differentiation into functional germ cells, gives reason for cautious optimism for future research.

Abbreviations:

• ART
• assisted reproductive technologies
• Bcl6b
• B-Cell CLL/Lymphoma 6B
• BMP4
• bone morphogenetic protein 4
• CD(24)(34)
• cluster of differentiation (24)(34)
• c-Kit
• KIT Proto-oncogene receptor tyrosine kinase
• FGF2
• Fibroblast growth factor 2
• FISH
• fluorescence in situ hybridisation
• GDNF
• glial cell line-derived neurotrophic factor
• ICSI
• intracytoplasmic sperm injection
• ID4
• inhibitor of differentiation 4
• KS
• Klinefelter syndrome
• PGC
• primordial germ cells
• PLZF
• promyelocytic leukaemia zinc finger
• PRISMA
• Preferred Reporting Items for Systematic Reviews and Meta-Analyses
• RA(R)
• retinoic acid (receptor)
• SSC
• spermatogonial stem cell
• SPG
• spermatogonia
• Stra8
• stimulated by RA 8
• ZBTB
• zinc finger and broad complex/Tramtrack/bric-a-brac

Keywords:

• Non-obstructive azoospermia
• Fertility preservation
• Onco-fertility
• Male infertility
• Stem cell therapy
• Allograft

Acknowledgements

Medical illustrator Vanessa Dudley.

Source of funding

Ryan Flannigan: American Urology Association New York Section E. Darracott Vaughan, Jr, MD, Research Scholar Award.

Conflict of interest

None.

Notes

Peer review under responsibility of Arab Association of Urology.