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  • 1
    In: HAMDAN MEDICAL JOURNAL, 2014
    ISSN: 2227-2437
    E-ISSN: 2227-247X
    Source: CrossRef
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  • 2
    In: Nature, 2006, Vol.440(7088), p.1199
    Description: Embryonic germ cells as well as germline stem cells from neonatal mouse testis are pluripotent and have differentiation potential similar to embryonic stem cells, suggesting that the germline lineage may retain the ability to generate pluripotent cells. However, until now there has been no evidence for the pluripotency and plasticity of adult spermatogonial stem cells (SSCs), which are responsible for maintaining spermatogenesis throughout life in the male. Here we show the isolation of SSCs from adult mouse testis using genetic selection, with a success rate of 27%. These isolated SSCs respond to culture conditions and acquire embryonic stem cell properties. We name these cells multipotent adult germline stem cells (maGSCs). They are able to spontaneously differentiate into derivatives of the three embryonic germ layers in vitro and generate teratomas in immunodeficient mice. When injected into an early blastocyst, SSCs contribute to the development of various organs and show germline transmission. Thus, the capacity to form multipotent cells persists in adult mouse testis. Establishment of human maGSCs from testicular biopsies may allow individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells. Furthermore, these cells may provide new opportunities to study genetic diseases in various cell lineages. [PUBLICATION ]
    Keywords: Stem Cells ; Adults ; Genetics ; Human ; Diseases ; Mice ; Derivatives ; Ethics ; General and Nonclassified (MD) ; General and Nonclassified (EC) ; General and Nonclassified (Ed) ; General and Nonclassified (Ep) ; Surveying, Theory, and Analysis (CE) ; Design Principles, Theory, and Analysis (Mt) ; Computing Milieux (General) (Ci) ; Electronics and Communications Milieux (General) (Ea) ; Solid State Milieux (General) (So) ; Article;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 3
    Language: English
    In: Stem Cell Reviews and Reports, 2012, Vol.8(3), pp.629-639
    Description: During the last few years, the Islamic republic of Iran has consistently grown in nearly all scientific fields and achieved considerable success in producing science and developing technology. The Iranian government and scientific community have jointly started programs to support the creation of new scientific opportunities and technology platforms for research in the domain of stem cell and tissue engineering. In addition, clinical translation of basic researches in the fields of stem cell and regenerative medicine has been amongst the top priorities. Interestingly, the public sector, media, and authorities are also actively monitoring these attainments. In spite of this nationwide interest, however, there is currently a dearth of analytical information on these accomplishments. To address this issue, here we introduce the key decisions made by the country’s policy makers and also review some of the Iranian researchers’ publications in this field.
    Keywords: Stem cell research ; Tissue engineering ; Iran ; Bibliometric analysis ; Ethics
    ISSN: 1550-8943
    E-ISSN: 1558-6804
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  • 4
    Language: English
    In: Stem cell reviews and reports, September 2012, Vol.8(3), pp.629-39
    Description: During the last few years, the Islamic republic of Iran has consistently grown in nearly all scientific fields and achieved considerable success in producing science and developing technology. The Iranian government and scientific community have jointly started programs to support the creation of new scientific opportunities and technology platforms for research in the domain of stem cell and tissue engineering. In addition, clinical translation of basic researches in the fields of stem cell and regenerative medicine has been amongst the top priorities. Interestingly, the public sector, media, and authorities are also actively monitoring these attainments. In spite of this nationwide interest, however, there is currently a dearth of analytical information on these accomplishments. To address this issue, here we introduce the key decisions made by the country's policy makers and also review some of the Iranian researchers' publications in this field.
    Keywords: Stem Cell Research -- Legislation & Jurisprudence
    ISSN: 15508943
    E-ISSN: 2629-3277
    E-ISSN: 15586804
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    Language: English
    In: In vitro cellular & developmental biology, 2015, Vol.51(10), pp.1093-1101
    Description: Human umbilical Wharton’s jelly-derived mesenchymal stem cells (HWJMSCs) are the best candidate to get plentiful stem cells and differentiate them to germ cells under appropriate conditions to treat infertility. We sought to determine under which conditions HWJMSCs could form male germ cells in vitro. So, HWJMSCs were differentiated to male germ cells under a mixture of bone morphogenetic protein-4 (BMP-4) and testicular and placental culture condition (TCC and PCC) medium followed by retinoic acid for 21 d. In the present study, the HWJMSCs were obtained from Wharton’s jelly of umbilical cords of male neonates delivered by cesarean section. At the third passage, mesenchymal stem cell markers and differentiation to osteocytes and adipocytes were investigated. Then, HWJMSCs were induced to differentiate into male germ cells in the presence of BMP-4, all-trans retinoic acid, PCC, and TCC for 21 d. The profile of c-Kit, DDX4, Piwil2, and Dazl gene expression was evaluated by qPCR and ICC. Data was analyzed by ANOVA test. After 3 wk of treatment with different reagents, the morphology of these spindle-like cells changed to shiny clusters and germ cell-specific markers in mRNA were upregulated in both TCC + retinoic acid (RA) and BMP-4 + RA. Induction of HWJMSCs with TCC in the presence of RA resulted in significant upregulation (P ≤ 0.05) of all germ cell-specific genes (c-Kit 2.6795 ± 0.75, DDX4 4.3188 ± 1.18, Piwil2 4.9962 ± 1.55, Dazl 6.1199 ± 0.78) compared to control and PCC + RA. Our results indicated that TCC and RA are involved in human germ cell development. Moreover, BMP signaling also induced differentiation. Our findings provide a novel effective approach for generation of germ cells in vitro and studying the interaction of germ cells with their niche. Our work represents an essential step toward gaining knowledge of the molecular properties of HWJMSCs in the field of cell therapy. We demonstrated that under a suitable situation, HWJMSCs have the ability to differentiate into germ cells and this provides an excellent pattern to study infertility cause and cure. ; p. 1093-1101.
    Keywords: Messenger Rna ; Genes ; Males ; Adipocytes ; Humans ; Gene Expression Regulation ; Germ Cells ; Retinoic Acid ; Stem Cells ; Neonates ; Analysis Of Variance ; Gene Expression ; Cesarean Section ; Quantitative Polymerase Chain Reaction
    ISSN: 1071-2690
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  • 6
    In: Microscopy Research and Technique, April 2017, Vol.80(4), pp.430-440
    Description: Studies published in recent years have changed the outlook on sterility and germ cell development by producing gametes from stem cells. In present study, a novel approach on differentiation of bone marrow‐derived stage‐specific embryonic antigen 1 positive (SSEA‐1) pluripotent stem cells into male germ cells has been addressed. SSEA‐1 stem cells were separated from murine bone marrow using magnetic‐activated cell sorting (MACS) system and propagated on a feeder layer cells. To evaluate the pluripotency characteristic of the purified cells, they were differentiated toward cells of three germ layers. Later the SSEA‐1 stem cells were induced to differentiate along male germ cell lineage with retinoic acid. Flowcytometric analysis of SSEA‐1 stem cells revealed purity of about 62% which increased to 91% after cultivation over feeder cells. Expression of specific transcripts of Oct4, SSEA‐1, Nanog, Dppa3, fragilis, Rex‐1, SOX‐2, and alkaline‐phosphatase and immunofluorescence evaluation of Oct4 and SSEA‐1 expression showed the differentiation of purified stem cells toward the cells of three germ layers. Differentiation potential of purified cells was positively evidenced by expression markers specific for primordial germ cells, spermatogonial stem cells and spermatogonia including Mvh, fragilis, Dppa3, Stra8, DAZL, Piwil2, β1, and α6‐integrins as well as meiotic‐specific marker SYCP3. Our results showed that SSEA‐1 pluripotent stem cells are able to differentiate into male germ cells. The results of the present study are encouraging enough to merit further investigation, provide a new hope for those suffering from infertility and introduce a novel platform for research on germ cell development. An available source for pluripotent stem cells as a substitute for embryonic stem cells was introduced. Pluripotent stem cells derived from an adult tissue were differentiated into male germ cells.
    Keywords: Fertility ; Gametogenesis ; Retinoic Acid ; Spermatogonial Stem Cells
    ISSN: 1059-910X
    E-ISSN: 1097-0029
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  • 7
    Language: English
    In: Iranian Journal of Basic Medical Sciences, 01 June 2013, Vol.16(6), pp.779-783
    Description:   Objective(s): Sertoli cells support in vivo germ cell production; but, its exact mechanism has not been well understood. The present study was designed to analyze the effect of Sertoli cells in differentiation of mouse embryonic stem cells (mESCs) to germ cells.   Materials and Methods: A fusion construct composed of a Stra8 gene promoter and the coding region of enhanced green fluorescence protein was produced to select differentiated mESCs. To analyze sertoli cells’ effect in differentiation process, mESCs were separated into two groups: the first group was cultured on gelatin with retinoic acid treatment and the second group was co-cultured with sertoli cell feeder without retinoic acid induction. Expressions of pre-meiotic (Stra8), meiotic (Dazl and Sycp3) and post-meiotic (Prm1) genes were evaluated at different differentiation stages (+7, +12 and +18 days of culture). Results: In the first group, expressions of meiotic and post-meiotic genes started 12 and 18 days after induction with retinoic acid, respectively. In the second group, 7 days after co-culturing with Sertoli cells, expression of meiotic and post-meiotic genes was observed. Conclusion: These results show that differentiation process to germ cells is supported by Sertoli cells. Our findings provide a novel effective approach for generation of germ cell in vitro and studying the interaction of germ cells with their niche.
    Keywords: Co-Culture Differentiation Embryonic Stem Cell In Vitro Derived Germ Cells Sertoli Cell ; Medicine
    ISSN: 2008-3866
    E-ISSN: 2008-3874
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  • 8
    In: Cell Research, 2008, Vol.18(S1), p.S26
    Description: Germ cells are highly specialized cells that form gametes, and they are the only cells within an organism that contribute genes to offspring. Germline stem cells (GSCs) sustain gamete production, both oogenesis (egg production) and spermatogenesis (sperm production), in many organisms. Since the genetic information contained within germ cells is passed from generation to generation, the germ line is often referred to as immortal. Therefore, it is possible that germ cells possess unique strategies to protect and transmit the genetic information contained within them indefinitely. On the other hand, it was shown that germ cells are pluripotent in all stages of development. We and other groups succeeded in the long-term culture of spermatogonial stem cells (SSCs) of mice. The cells were phenotypically similar to the ES/embryonic germ cells except for their genomic imprinting pattern. They differentiated into various types of somatic cells in vitro under the conditions used to induce the differentiation of the ES cells, and the SSCs formed germline chimeras when injected into blastocysts. Furthermore, we have shown that somatic stem cells are able to differentiate to germ cells. Derivation of both male and female gametes in vitro raises the possibility of using these gametes to gain a better understanding of basic reproductive biology and, in particular, to extend the potential for therapeutic cloning, transgenic technologies and the treatment of infertility. We started three different approaches for establishment of the in vitro gametogenesis systems: 1) ES-derived gametogenesis, 2) derivation of germ cells from somatic stem cells and 3) in vitro gametogenesis based on cultured spermatogonial stem cells. We developed a strategy for the establishment of germline stem cell lines from embryonic stem cells. These cells are able to undergo meiosis, generate haploid male gametes in vitro and are functional, as shown by fertilization after intra-cytoplasmic injection into mouse oocytes. Molecular and cellular mechanisms underlying differentiation of ES to functional gametes should be elucidated in future research. In other approach, we show that bone marrow stem (BMS) cells are able to trans-differentiate into male germ cells. BMS cell-derived germ cells expressed the known molecular markers of primordial germ cells. Based on these data and published data from different group, we will discuss these data and present a hypothesis that some somatic stem cells could be direct descendants of the germ lineage. The germ lineage in order to pass genes on to the next generations creates soma and thus becomes a 'mother lineage' for all somatic stem cell lineages present in the adult body.
    Keywords: Biology;
    ISSN: 1001-0602
    E-ISSN: 17487838
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  • 9
    In: Cell Research, 2007, Vol.17(11), p.895
    Description: The continuation of the spermatogenic process throughout life relies on a proper regulation of self-renewal and differentiation of germline testis stem cells, the spermatogonial stem cells. These are single cells situated on the basal membrane of the seminiferous epithelium. Only 0.03% of all germ cells are spermatogonial stem cells (SSCs) 1, 2, 3. To maintain spermatogenesis, the processes of self-renewal and differentiation of SSCs must be precisely regulated by intrinsic gene expression in the stem cells and extrinsic signals, including soluble factors or adhesion molecules from the surrounding microenvironment, the stem cell niche.Spermatogonial stem cells are descendants of the primordial germ cells (PGCs), which migrate from extra-embryonic sites to colonize the gonadal ridge early during embryonic life. In the females, the primordial germ cells proliferate extensively and enter meiotic prophase at around the time of birth. In males, cessation of germ cell proliferation and blockade of meiotic entry are important steps in the morphogenetic cascade initiated by the expression of the SRY gene. The male germ cells associate with somatic cells of the presumptive gonad and form testicular cords, which mark the differentiation of PGCs into gonocytes. Different stages of germ cell development to spermatogonial stem cells are shown in Figure 1.Several lines of evidence have suggested extensive proliferation activity and pluripotency of germline stem cells, including spermatogonial stem cells.In an early embryo a cell has the potential to generate many different cell types. During development cells generally lose this potential or 'potency', and become restricted to making one or a few cell types. Cells can become undetermined and undifferentiated in special circumstances. These undifferentiated cells which are capable of self-renewal and differentiation into more specialized cells are termed as stem cells 4, 5. Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. Embryonic stem cells, as their name suggests, are derived from embryos.There are several lines of evidence which show the potency of germ cells in prenatal and postnatal stages. Cultured PGCs exposed to a specific cocktail of growth factors give rise to embryonic germ cells, pluripotent stem cells that can contribute to all the lineages of chimeric embryos including the germline. The conversion of PGCs into pluripotent stem cells is a remarkably similar process to nuclear reprogramming in which a somatic nucleus is reprogrammed in the egg cytoplasm. The conversion of PGCs into pluripotent stem cells may be linked in some way with their deregulated proliferation 6, 7. Other evidence is the pluripotency of testicular germ cell tumors. Testicular teratomas are highly unusual benign tumors containing derivatives of the three primary germ layers. Different studies have shown that embryonal carcinomas (EC) are derived from PGCs 8. Assays of developmental potency show that isolated EC cells are pluripotent stem cells, but when they lose the ability to differentiate they form malignant teratocarcinomas. Understanding the genetics of embryonal carcinoma cell formation and the growth factor signaling pathways controlling embryonic germ cell derivation could tell us much about the molecular controls on developmental potency in mammals 9, 10.After birth, two stages of germline stem cell differentiation have been discussed: neonatal and adult stages. Cells isolated from neonatal testis are able to differentiate to the cells of all three germ layers 11, 12, including mesodermal cells, namely cardiomyocytes and endothelial cells and therefore these cells are termed as multipotent germline stem cells (mGSCs, Figure 1). In adult, germline stem cells develop to spermatogonial stem cells or spermatogonial progenitor cells. Recently, two groups showed successful isolation, culture and characterization of these cells 13, 14, 15. The first group used a genetic selection strategy using a spermatogonial specific promoter (Stra8) and green fluorescence protein (GFP) to isolate the cells from adult mouse testis. They were able to isolate and culture these cells in culture medium containing the precise combination of cellular growth factors needed for the cells to reproduce themselves in vitro 13. These cells called multipotent adult germline stem cells (maGSCs) are pluripotent (Figure 1). More recently, the group of Shahin Rafii could confirm the pluripotency of spermatogonial stem cells and were able to isolate these cells by a specific surface maker, GPR125. Expr
    Keywords: Biology;
    ISSN: 1001-0602
    E-ISSN: 17487838
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  • 10
    In: Developmental Biology, May 15, 2001, Vol.233(2), p.319
    Description: Spermatid perinuclear RNA-binding protein (SPNR) is a microtubule-associated RNA-binding protein that localizes to the manchette in developing spermatids. The Spnr mRNA is expressed at high levels in testis, ovary, and brain and is present in these tissues in multiple forms. We have generated a gene trap allele of the murine Spnr, named [Spnr.sup.+/GT]. [Spnr.sup.GT/GT] mutants show a high rate of mortality, reduced weight, and an abnormal clutching reflex. In addition to minor anatomical abnormalities in the brain, males exhibit defects in spermatogenesis that include a thin seminiferous epithelium and disorganization of spermatogenesis. Most of the sperm from mutant males display defects in the flagellum and consequently show decreased motility and transport within the oviducts. Furthermore, sperm from mutant males achieve in vitro fertilization less frequently. Our findings suggest that SPNR plays an important role in normal spermatogenesis and sperm function. Thus, the [Spnr.sup.GT/GT] mutant male mouse provides a unique model for some human male infertility cases. [C] 2001 Academic Press Key Words: Spnr; gene trap; sperm; flagellum; brain; nervous system; mouse; microtubule-associated protein.
    Keywords: Sperm -- Genetic Aspects ; Neurogenetics -- Genetic Aspects ; Brain Abnormalities
    ISSN: 0012-1606
    Source: Cengage Learning, Inc.
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