Format

Send to

Choose Destination
Stem Cells Transl Med. 2014 Sep;3(9):1043-54. doi: 10.5966/sctm.2014-0045. Epub 2014 Jul 18.

Testicular niche required for human spermatogonial stem cell expansion.

Author information

1
Departments of Urology and Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA; Helen Schneider Hospital for Women, Rabin Medical Center, Petah-Tiqva, Israel; Department of Obstetrics and Gynecology, Albert Einstein University, Bronx, New York, USA.
2
Departments of Urology and Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA; Helen Schneider Hospital for Women, Rabin Medical Center, Petah-Tiqva, Israel; Department of Obstetrics and Gynecology, Albert Einstein University, Bronx, New York, USA trann@obgyn.ucsf.edu.

Abstract

Prepubertal boys treated with high-dose chemotherapy do not have an established means of fertility preservation because no established in vitro technique exists to expand and mature purified spermatogonial stem cells (SSCs) to functional sperm in humans. In this study, we define and characterize the unique testicular cellular niche required for SSC expansion using testicular tissues from men with normal spermatogenesis. Highly purified SSCs and testicular somatic cells were isolated by fluorescence-activated cell sorting using SSEA-4 and THY1 as markers of SSCs and somatic cells. Cells were cultured on various established niches to assess their role in SSC expansion in a defined somatic cellular niche. Of all the niches examined, cells in the SSEA-4 population exclusively bound to adult testicular stromal cells, established colonies, and expanded. Further characterization of these testicular stromal cells revealed distinct mesenchymal markers and the ability to undergo differentiation along the mesenchymal lineage, supporting a testicular multipotent stromal cell origin. In vitro human SSC expansion requires a unique niche provided exclusively by testicular multipotent stromal cells with mesenchymal properties. These findings provide an important foundation for developing methods of inducing SSC growth and maturation in prepubertal testicular tissue, essential to enabling fertility preservation for these boys.

KEYWORDS:

Cancer; Cell surface markers; Clinical translation; Mesenchymal stem cells; Spermatogonial stem cells

PMID:
25038247
PMCID:
PMC4149303
DOI:
10.5966/sctm.2014-0045
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center