Enrichment and Differentiation of Human Germ-Like Cells Mediated by Feeder Cells and Basic Fibroblast Growth Factor Signaling

West, Franklin D.; Machacek, Dave W.; Boyd, Nolan L.; Pandiyan, Kurinji; Robbins, Kelly R.; Stice, Steven L.

doi:10.1634/stemcells.2008-0124

Cited by 95 publications

(84 citation statements)

References 59 publications

(88 reference statements)

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“…Induced germ cell differentiation protocols can be divided into two main groups. In one group of protocols, specific factors are added to the differentiating cells in order to increase germ cell derivation (BMP4 [5,[10][11][12], retinoic acid (RA) [7,[13][14][15], basic fibroblast growth factor (bFGF) [16], testicular cell conditioned medium [14,17], forskolin [15] and wingless-related MMTV integration site 3A (Wnt3a) [11]). Other protocols focus on the selection and enrichment of the spontaneously derived germ cell population [6,18,19].…”

Section: Introductionmentioning

confidence: 99%

Sertoli cell-conditioned medium induces germ cell differentiation in human embryonic stem cells

Geens

Sermon

Velde

et al. 2011

J Assist Reprod Genet

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Purpose To investigate the spontaneous germ cell differentiation capacity of VUB hESC lines, develop a protocol for the induction of germ cell differentiation using conditioned medium from Sertoli cells (SCCM) and compare it to existing protocols. Methods hESC were allowed to differentiate spontaneously or after the addition of bone morphogenetic proteins (BMPs) and/or SCCM. VASA transcripts were measured by relative quantification real-time RT-PCR to determine the efficiency of germ cell differentiation. Results VUB hESC lines can differentiate spontaneously towards the germ cell lineage, however, more consistently in an embryoid body approach than in monolayer cultures.BMPs and SCCM significantly improve VASA expression, but do not have a synergistic effect. Direct contact of differentiating hESC with Sertoli cells does not improve VASA expression. Conclusions SCCM contains inductive factors for germ cell differentiation and could represent an element for in-vitro differentiation to germ cells.

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Section: Introductionmentioning

confidence: 99%

Sertoli cell-conditioned medium induces germ cell differentiation in human embryonic stem cells

Geens

Sermon

Velde

et al. 2011

J Assist Reprod Genet

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“…Co-culture systems and conditioned medium have been used to recapitulate the gonadal microenvironment for differentiation of germ cells. Co-cultures containing fetal gonadal stromal cells [62], Sertoli cells [63], or embryonic fibroblasts [64] increase the differentiation of pluripotent stem cells to PGCs. Although these co-culture systems may produce the desired results, induction with chemically or biologically defined factors is preferred, because it increases the safety of cells for clinical applications and improves the reproducibility of the differentiation process.…”

Section: Recent Advances In the Germ Cell Differentiation From Ips Cellsmentioning

confidence: 99%

Induced pluripotent stem cells in reproductive medicine

Teramura

Frampton

2012

Reprod Medicine & Biology

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Despite recent advances in reproductive medicine, there are still no effective treatments for severe infertility caused by congenital absence of germ cells or gonadotoxic treatments during prepubertal childhood. However, the development of technologies for germ cell formation from stem cells in vitro, induction of pluripotency from somatic cells, and production of patient-specific pluripotent stem cells may provide new solutions for treating these severe fertility problems. It may be possible to produce germ cells in vitro from our own somatic cells that can be used to restore fertility. In addition, these technologies may also bring about novel therapies by helping to elucidate the mechanisms of human germ cell development. In this review, we describe the current approaches for obtaining germ cells from pluripotent stem cells, and provide basic information about induction of pluripotency and germ cell development.

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“…Growth factors such as bone morphogenetic protein and others play a critical role in inducing germ cell differentiation from hESCs. [58][59][60][61] To date, in vitro models using hESCs have produced post-meiotic spermatids, 62 but complete spermatogenesis with mature sperm has yet to be reported.…”

Section: From Embryonic Stem Cells To Germ Cellsmentioning

confidence: 99%

Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models

Lo¹,

Domes²

2011

Asian J Androl

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There have been tremendous advances in both the diagnosis and treatment of male factor infertility; however, the mechanisms responsible to recreate spermatogenesis outside of the testicular environment continue to elude andrologists. Having the ability to 'grow' human sperm would be a tremendous advance in reproductive biology with multiple possible clinical applications, such as a treatment option for men with testicular failure and azoospermia of multiple etiologies. To understand the complexities of human spermatogenesis in a research environment, model systems have been designed with the intent to replicate the testicular microenvironment. Currently, there are both in vivo and in vitro model systems. In vivo model systems involve the transplantation of either spermatogonial stem cells or testicular xenographs. In vitro model systems involve the use of pluripotent stem cells and complex coculturing and/or three-dimensional culturing techniques. This review discusses the basic methodologies, possible clinical applications, benefits and limitations of each model system. Although these model systems have greatly improved our understanding of human spermatogenesis, we unfortunately have not been successful in demonstrating complete human spermatogenesis outside of the testicle. Asian Journal of Andrology (2011) 13, 677-682; doi:10.1038/aja.2011.88; published online 18 July 2011 Keywords: fertility preservation; spermatogenesis models; spermatogonial stem cells INTRODUCTIONRecreating human spermatogenesis outside of its original environment remains the 'Holy Grail' for generations of andrologists. To grow sperm is not only a matter of scientific curiosity, but also a quest for the treatment of male infertility. A well-characterized model for spermatogenesis in humans will have a huge impact on our understanding on the physiological and genetic pathways of male reproduction. Its clinical applications also extend to the study of human reproductive toxicology and preservation of fertility in treated cancer patients.While significant progress has been made in the laboratory, multiple obstacles remain. Current knowledge on the control of gonadogenesis, spermatogenesis and steroidogenesis are based on the examination of histology, immunohistochemistry, hormonal assays, and phenotypes of single gene or small groups of gene alterations in animal models. Human studies in male reproduction are hindered by the lack of human testicular specimens, which are not as readily available as our animal counterparts, for ethical and practical reasons. In this review, we will examine the existing literature on the experimental models and their limitations in growing sperm to provide a foundation for future investigation and clinical application ( Table 1).

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Enrichment and Differentiation of Human Germ-Like Cells Mediated by Feeder Cells and Basic Fibroblast Growth Factor Signaling

Abstract: ABSTRACT

Cited by 95 publications

References 59 publications

Sertoli cell-conditioned medium induces germ cell differentiation in human embryonic stem cells

Sertoli cell-conditioned medium induces germ cell differentiation in human embryonic stem cells

Induced pluripotent stem cells in reproductive medicine

Can we grow sperm? A translational perspective on the current animal and human spermatogenesis models

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