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Preserving male fertility with spermatogonial stem cells

Valli, Hanna (2014) Preserving male fertility with spermatogonial stem cells. Doctoral Dissertation, University of Pittsburgh.

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Abstract

Improved therapies for cancer and other conditions have resulted in a growing population of long-term survivors. Infertility is an unfortunate side effect of some cancer therapies that impacts the quality of life of survivors who are in their reproductive or pre-reproductive years. Some of these patients have the opportunity to preserve their fertility using standard technologies that include sperm, egg or embryo banking, followed by in vitro fertilization and/or embryo transfer. However, these options are not available to all patients, especially the prepubertal patients who are not yet producing mature gametes. For these patients, there are several stem cell technologies in the research pipeline that may give rise to new fertility options and allow infertile patients to have their own biological children. Spermatogonial stem cells are the foundation of spermatogenesis and may have application for preserving and restoring male fertility. However, majority of the knowledge about spermatogonial stem cells (SSCs) comes from rodents and not much is known about humans. In Chapter 2, I demonstrate that human spermatogonia have the phenotype of UTF1+, SALL4+, ENO2+, UCHL1+, ZBTB16+, ITGA6+, THY1 dim, EPCAM dim, KIT- and that using the cell surface markers ITGA6, THY1, EPCAM it is possible to enrich human SSCs. In Chapter 3, I used this knowledge about the phenotype of human spermatogonia to show that the best method to cryopreserve intact human testicular pieces is controlled slow-freezing. In Chapter 4, I used the phenotype of human spermatogonia from Chapter 2, to show that it is possible to separate potentially therapeutic human spermatogonial stem cells from malignant contamination. This is important because a majority of our prepubertal patients will have a testicular biopsy taken prior to initiation of chemotherapy so we want to make sure there would be no malignant contamination in the sample. Progress represented by this thesis research will facilitate translating SSC technologies toward the clinic for preservation and restoration of male fertility.


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Details

Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Valli, Hannavallihan@pitt.eduVALLIHAN
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorOrwig, Kyle Ekorwig@mwri.magee.edu
Committee MemberBadylak, Stephen Fbadysx@upmc.edu
Committee MemberFunderburgh, James Ljlfunder@pitt.eduJLFUNDER
Committee MemberWalker, William Hwalkerwh@mwri.magee.eduWALKERW
Date: 29 October 2014
Date Type: Publication
Defense Date: 30 September 2014
Approval Date: 29 October 2014
Submission Date: 28 October 2014
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 114
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: spermatogonial stem cells, testis, infertility, spermatogenesis
Date Deposited: 29 Oct 2014 14:36
Last Modified: 19 Dec 2016 14:42
URI: http://d-scholarship.pitt.edu/id/eprint/23425

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