Potentiality of Marrow-Derived Mesenchymal Stem Cells Isolated from EGFP Transgenic-Mice and Pigs Differentiate into Testicular Cells
Date Issued
2009
Date
2009
Author(s)
Liu, Hui-Yu
Abstract
According to the World Health Organization (2005) reports, there are 15% of couples suffered from infertility worldwide; majority is on the male factors. In clinical, chemotherapy is one of the major causes of male infertility, where the somatic cells, including germ cells, are decreased within the process. To this end, embryonic stem cells have been used in treating testicular failures recently, regards to their self-renewal and pluripotent characteristics. However, ethical concerns have made it difficult. n this study, the regenerative and therapeutic functions of postnatal bone marrow mesenchymal stem cells (MSCs) were examined in mice with testicular failure. Followed by treatments of retinoic acid (RA, 10-6 M) for 21 days, the male germ cells markers, including Stra8, piwil2, Tex14 and Dazl could be significantly induced from the MSCs cultures, confirmed by RT-PCR assay. To validate their potential in vivo, MSCs isolated from mouse (EGFP-mMSCs) and pig (EGFP-pMSCs) expressing foreign EGFP (enhanced green fluorescent protein) gene, for tracking purpose, MSCs were injected into seminiferous tubules and the testicular interstitium of the busulfan-treated mice in an allogenic and xenogenic manner respectively. With evidenced by epifluorescence microscopy, the GFP positive MSCs was observed within the seminiferous structure after 2~3 months of transplantation. As well, some of the injected EGFP-mMSCs expressed the male germ cells specific maker VASA, and leydig cells maker P450scc, while the EGFP-pMSCs exhibited lower expression patterns. Functional analyses demonstrated that the production of testosterone in both EGFP-mMSCs and EGFP-pMSCs treated mice were significantly increased. In addition, their fertilities were also enhanced as compared with the untreated mice after one month.ollectively, we demonstrated that marrow-derived MSCs of mouse and pig possess the potential to differentiate into testicular cells both in vitro and in vivo. This clinical relevant finding raises the possibility for treatment of male infertility and testosterone deficiency through the therapeutic use of MSCs eywords: Male infertility, mesenchymal stem cells, male germ cells, testicular cells, leydig cell
Subjects
Male infertility
mesenchymal stem cells
male germ cells
testicular cells
leydig cell
Type
thesis
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