Therapeutic Advances
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2016; 8(10): 306-315
Published online Oct 26, 2016. doi: 10.4252/wjsc.v8.i10.306
Stem cell therapy for the treatment of Leydig cell dysfunction in primary hypogonadism
Taylor C Peak, Nora M Haney, William Wang, Kenneth J DeLay, Wayne J Hellstrom
Taylor C Peak, Nora M Haney, William Wang, Kenneth J DeLay, Wayne J Hellstrom, Department of Urology, School of Medicine, Tulane University, New Orleans, LA 70112, United States
Author contributions: All the authors contributed to the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wayne J Hellstrom, MD, Department of Urology, School of Medicine, Tulane University, 1430 Tulane Ave. 8642, New Orleans, LA 70112, United States. whellst@tulane.edu
Telephone: +1-504-9883361 Fax: +1-504-9885059
Received: May 3, 2016
Peer-review started: May 3, 2016
First decision: June 13, 2016
Revised: July 27, 2016
Accepted: August 27, 2016
Article in press: August 29, 2016
Published online: October 26, 2016
Processing time: 170 Days and 6.9 Hours
Abstract

The production of testosterone occurs within the Leydig cells of the testes. When production fails at this level from either congenital, acquired, or systemic disorders, the result is primary hypogonadism. While numerous testosterone formulations have been developed, none are yet fully capable of replicating the physiological patterns of testosterone secretion. Multiple stem cell therapies to restore androgenic function of the testes are under investigation. Leydig cells derived from bone marrow, adipose tissue, umbilical cord, and the testes have shown promise for future therapy for primary hypogonadism. In particular, the discovery and utilization of a group of progenitor stem cells within the testes, known as stem Leydig cells (SLCs), has led not only to a better understanding of testicular development, but of treatment as well. When combining this with an understanding of the mechanisms that lead to Leydig cell dysfunction, researchers and physicians will be able to develop stem cell therapies that target the specific step in the steroidogenic process that is deficient. The current preclinical studies highlight the complex nature of regenerating this steroidogenic process and the problems remain unresolved. In summary, there appears to be two current directions for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells into testicular tissue. Theoretically, in-vivo re-activation of SLCs in men with primary hypogonadism due to age would be another alternative method to treat hypogonadism while eliminating the need for transplantation.

Keywords: Stem cell therapy; Leydig cells; Primary hypogonadism; Stem Leydig cells; Testosterone; Bone marrow-derived stem cells; Adipose-derived mesenchymal stem cells

Core tip: Although clinicians are capable of treating primary hypogonadism with exogenous testosterone, there is no therapy that mimics its physiologic release. Two current directions exist for stem cell therapy in male primary hypogonadism. The first method involves differentiating adult Leydig cells from stem cells of various origins from bone marrow, adipose, or embryonic sources. The second method involves isolating, identifying, and transplanting stem Leydig cells (SLCs) into testicular tissue. Re-activation of SLCs in men with primary hypogonadism due to age would also be an alternative method. As researchers are better able to replicate the differentiation process of androgenic tissue, treatments will hopefully follow.