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Background: Some research studies provided evidence for the differentiation capacity of adult stem cells (ASCs) into germ cells (GCs). Since the generation of GCs from stem cells (SCs) has been proposed as a potential way for treatment of infertility, many research groups have begun their creative studies on generation of new GCs both in vitro and in vivo, and utilized different ASC types such as bone marrow mesenchymal stem cells (BM-MSCs), skin stem cells, pancreatic stem cells, and adipose tissue MSCs. Despite many interesting reports with promising results, an obvious problem in the research projects was the functionality of the produced GCs., Objective: In this paper, we have reviewed the results of almost all previously published reports on derivation of male and female GCs from ASCs to provide a better insight into this field of research., Results: The most evaluated papers have shown that ASCs from various tissues can differentiate into GCs but rarely were the produced GCs functional and could form fertile gametes neither in vitro, nor in vivo (after transplantation into the gonads)., Conclusion: There are still so many unknown issues about gametogenesis. Perhaps making alterations in treatment methods and utilizing creative techniques like tissue engineering and gene targeting help to achieve a standard method of in vitro GC production from ASCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Mesenchymal stem cells (MSCs) have the capacity to differentiate into germ cells (GCs). This research, for the first time, has evaluated the fate of in vitro MSC-derived GCs generated by three different induction methods and compared them after transplantation into the testes of rams. Passage-3 ram bone marrow (BM)-MSCs were divided into three treatment groups: (1) 14-d treatment with 10 μM retinoic acid (RA; RA14), (2) 21-d treatment with 10 μM RA (RA21), and (3) 21-d treatment with 10 ng/ml transforming growth factor beta-1 (TGFb1). After confirmation of the existence of germ-like cells in the culture, the treated cells were labeled and transplanted into the testes of ram lambs. After 2 mo, we conducted histological evaluations of the rams' testes. Results showed that in vitro-derived GCs from all treatment groups survived in the testes. Some of these GCs homed at the basement membrane of seminiferous tubules and formed colonies. The homed cells and cell colonies were similar to testicular native spermatogonia and expressed PGP9.5. TGFb1 exhibited the highest efficiency for in vitro production of GCs as well as the highest capability for homing and colony formation in the testes. RA21 was less efficient than TGFb1, particularly in colony formation. RA14 was the weakest group. No further differentiation of the transplanted GCs was observed. From our results, it could be concluded that a 21-d treatment period of BM-MSCs with TGFb1 is the most efficient method for in vitro generation of spermatogonia-like cells that survive, home, and form colonies in the testes.

Recent studies have shown that mesenchymal stem cells (MSCs), under appropriate conditions, can differentiate into cell types including germ cells (GCs). These studies also show that MSCs without any induction express some GC-specific genes innately. Moreover, one report suggests that female MSCs have a greater tendency to differentiate into female instead of male GCs. Therefore, for the first time, this study attempts to assay and determine the differences between the expression levels of some important GC-specific genes (Stra8, Vasa, Dazl, Stella, Piwil2, Oct4, Fragilis, Rnf17 and c-Kit) in male and female bone marrow (BM)-MSCs of rats. BM sampling of the rate was performed by a newly established method. We cultured rat BM samples, then characterized male and female MSCs according to their adhesion onto the culture dish, their differentiation potential into bone, cartilage and fat cells, and phenotype analysis by flow cytometry. The expression of GC-specific genes and their expression levels were evaluated with reverse transcription polymerase chain reaction (RT-PCR) and real-time RT-PCR. Our results showed that Dazl and Rnf17 did not express in the cells. The majority of examined genes, except Piwil2, expressed at almost the same levels in male and female MSCs. Piwil2 had higher expression in male MSCs which was probably related to the more prominent role of Piwil2 in the male GC development process. Male BM-MSCs appeared more prone to differentiate into male rather than female GCs. Additional research should be performed to determine the exact role of different genes in the male and female GC development process.

Contents Several studies have proposed that in vitro generation of germ cells ( GCs) from stem cells can be considered a future option for infertility treatment. Mesenchymal stem cells ( MSCs) have the capability to differentiate into male GCs with the use of inducers such as retinoic acid. Transforming growth factor-beta 1 ( TGFb1) has been shown to play important roles in male fertility and spermatogenesis. Bone morphogenic protein 4 ( BMP4) and BMP8b are also involved in the derivation of primordial GCs ( PGCs) from epiblast cells. Therefore, this study aims to determine whether TGFb1, BMP4 and BMP8b can initiate transdifferentiation of MSCs into GCs in vitro and to determine the type of changes that occur in the expression of GC-specific markers. In this study, we have divided passage-3 ram bone marrow ( BM)- MSCs into three main groups ( BMP4, BMP8b and TGFb1) which were separately treated with 10 ng/ml TGFb1, 100 ng/ml BMP4 and 100 ng/ml BMP8b for a period of 21 days. We have evaluated the ability of these groups to differentiate into GCs by assessing expressions of GC-specific markers with reverse transcription PCR ( RT- PCR), quantitative RT- PCR ( qRT- PCR), immunocytochemistry, morphological changes and alkaline phosphatase ( ALP) activity. Our results showed that BMP4 and BMP8b induced PGCs properties in some BM- MSCs and TGFb1 formed spermatogonial stem cells ( SSCs) and spermatogonia-like cells in BM- MSCs culture. The important results of this study provide the basis for additional studies to determine the exact mechanism of GCs differentiation and possibly solve the problem of infertility. [ABSTRACT FROM AUTHOR]