The Regenerative Effect of Bone Marrow-Derived Stem Cells in Spermatogenesis of Infertile Hamster

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Abstract

BACKGROUND

Infertility is a serious social problem in advanced nations, with male factor in half of all cases of infertility. This study was conducted to determine the regenerative effect of bone marrow-derived stem cells in spermatogenesis of infertile hamster.

METHODS

Twelve adult male hamsters were equally divided into azoospermic and control groups. Busulfan was intraperitoneally used for induction of azoospermia, while the right testis was treated with bone marrow-derived stem cells (10 ⁶ BM-SCs), labeled with sterile trypan blue, 35 days after busulfan injection. The left testis served as positive control for azoospermia. Sixty days after cell transplantation, the animals were euthanized and both testes were removed and evaluated histologically.

RESULTS

BM-SCs were spindle-shaped, adherent to the culture flasks and had positive expression of CD29 and CD73 and negative expression of CD45. Alcian blue staining confirmed differentiation of BM-SCs into chondrocytes. Karyotyping denoted to stability of chromosomes. Treatment with busulfan in seminiferous tubules resulted into distruption of spermatogenesis. After two months in busulfan treatment group, seminiferous tubular atrophy and germinal epitheliums degenerations were noticed with no spermatozoa in epididymis. After treatment of busulfan group with BM-SCs, spermatogonia, primary spermatocytes, spermatids and sperms were present in seminiferous tubules.

CONCLUSION

As cell transplantation in seminiferous tubules resulted into a rapid repair of pathological changes, BM-SCs can be recommended an effective treatment measure in azoospermia. It seems that more studies are necessary to confirm the use of this technique in treatment of azoospermia and infertility in human.

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Most cited references 34

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Evaluation of the azoospermic patient.

J P Jarow, M Espeland, L I Lipshultz (1989)

Azoospermia is found in up to 10 to 20 per cent of the men who present to an infertility clinic. The main causes are testicular failure and ductal obstruction. Testicular biopsy remains the definitive test used to differentiate these 2 disorders. A retrospective study of 133 azoospermic men was performed to determine the accuracy and limitations of noninvasive variables in predicting testicular failure in an effort to limit the need for diagnostic testicular biopsy. Of 49 patients (37 per cent) with ductal obstruction a third had bilateral vasal agenesis. The remaining 84 azoospermic patients (63 per cent) had testicular failure. The results of the complete evaluation of these patients are described. Among the 101 patients with a testicular biopsy confirmed diagnosis there was a significant difference in testicular size (p less than 0.001), ejaculate volume (p less than 0.001) and serum follicle-stimulating hormone (p less than 0.001) between patients with testicular failure and those with ductal obstruction. The sensitivity and specificity of various parameters were determined. The best criteria to predict ductal obstruction preoperatively are a serum follicle-stimulating hormone level of less than 2 times greater than normal and the absence of bilateral testicular atrophy (100 per cent sensitivity and 71 per cent specificity). An algorithm for evaluation of the azoospermic patient is described such that all men with ductal obstruction and a minimal number with testicular failure undergo testicular biopsy.

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The genetic causes of male factor infertility: a review.

Katherine O'Flynn O'Brien, Alex Varghese, Ashok Agarwal (2010)

To illustrate the necessity for an enhanced understanding of the genetic basis of male factor infertility, to present a comprehensive synopsis of these genetic elements, and to review techniques being utilized to produce new insights in fertility research. Male factor infertility is a complex disorder that affects a large sector of the population; however, many of its etiologies are unknown. By elucidating the underlying genetic basis of infertile phenotypes, it may be possible to discover the causes of infertility and determine effective treatments for patients. The PubMed database was consulted for the most relevant papers published in the last 3 years pertaining to male factor infertility using the keywords "genetics" and "male infertility." Advances have been made in the characterization of the roles of specific genes, but further research is necessary before these results can be used as guidelines for diagnosing and treating male factor infertility. The accurate transmission of epigenetic information also has considerable influence on fertility in males and on the fertility of their offspring. Analysis of the genetic factors that impact male factor infertility will provide valuable insights into the creation of targeted treatments for patients and the determination of the causes of idiopathic infertility. Novel technologies that analyze the influence of genetics from a global perspective may lead to further developments in the understanding of the etiology of male factor infertility through the identification of specific infertile phenotype signatures. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium.

Massimiliano Gnecchi, Renata G L Melo (2008)

Mesenchymal stem cells (MSCs) are defined as self-renewing and multipotent cells capable of differentiating into multiple cell types, including osteocytes, chondrocytes, adipocytes, hepatocytes, myocytes, neurons, and cardiomyocytes. MSCs were originally isolated from the bone marrow stroma but they have recently been identified also in other tissues, such as fat, epidermis, and cord blood. Several methods have been used for MSC isolation. The most common method is based on the ability of the MSCs to selectively adhere to plastic surfaces. Phenotypic characterization of MSCs is usually carried out using immunocytochemical detection or fluorescence-activated cell sorting (FACS) analysis of cell surface molecule expression. However, the lack of specific markers renders the characterization of MSCs difficult and sometimes ambiguous. MSCs posses remarkable expansion potential in culture and are highly amenable to genetic modification with various viral vectors rendering them optimal vehicles for cell-based gene therapy. Most importantly, MSC plasticity and the possibility to use them as autologous cells render MSCs suitable for cell therapy and tissue engineering. Furthermore, it is known that MSCs produce and secrete a great variety of cytokines and chemokines that play beneficial paracrine actions when MSCs are used for tissue repair. In this chapter, we describe methods for isolation, ex vivo expansion, phenotypic characterization, and viral infection of MSCs from mouse bone marrow. We also describe a method for preparation of conditioned and concentrated conditioned medium from MSCs. The conditioned medium can be easily tested both in vitro and in vivo when a particular paracrine effect (i.e., cytoprotection) is hypothesized to be an important mechanism of action of the MSCs and/or screened to identify a target paracrine/autocrine mediator.

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Author and article information

Journal

Journal ID (nlm-ta): World J Plast Surg

Journal ID (iso-abbrev): World J Plast Surg

Journal ID (publisher-id): WJPS

Title: World Journal of Plastic Surgery

Publisher: Iranian Society for Plastic Surgeons (Tehran, Iran )

ISSN (Print): 2228-7914

ISSN (Electronic): 2252-0724

Publication date (Print): January 2017

Volume: 6

Issue: 1

Pages: 18-25

Affiliations

[1 ]Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;

[2 ]Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

Author notes

[* ]Corresponding Author: Akbar Vahdati, PhD; Professor of Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran, Tel: +98-71-32341025, Email: avahdatim@yahoo.com

Article

Publisher ID: wjps-6-018

PMC ID: 5339605

PubMed ID: 28289609

SO-VID: 8b9ac0a0-08e3-4b27-9fd7-63be91525552

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Regenerative Effect of Bone Marrow-Derived Stem Cells in Spermatogenesis of Infertile Hamster

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Abstract

BACKGROUND

METHODS

RESULTS

CONCLUSION

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Universal stem cells

Most cited references 34

Evaluation of the azoospermic patient.

The genetic causes of male factor infertility: a review.

Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium.

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