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Mammalian females ovulate periodically over their reproductive lifetimes, placing significant demands on their ovaries for egg production. Whether mammals generate new eggs in adulthood using stem cells has been a source of scientific controversy. If true, these "germ-line stem cells" might allow novel treatments for infertility and other diseases. However, new research from Carnegie's Lei Lei and Allan Spradling demonstrates that adult mice do not use stem cells to produce new eggs. Their work is published by the Proceedings of the National Academy of Sciences the week of April 29.

Before birth, mouse and human ovaries contain an abundant supply of germ cells, some of which will develop into the eggs that will ultimately be released from follicles during ovulation. Around the time of birth these germ cells have formed a large reserve of primordial follicleseach containing a single immature egg. Evidence of new follicle production is absent after birth, so it has long been believed that the supply of follicles is fixed at birth and eventually runs out, leading to menopause.

During the last decade, some researchers have claimed that primordial follicles in adult mouse ovaries turn over and that females use adult germ-line stem cells to constantly resupply the follicle pool and sustain ovulation. These claims were based on subjective observations of ovarian tissue and on the behavior of extremely rare ovarian cells following extensive growth in tissue culture, a procedure that is capable of "reprogramming" cells.

Lei and Spradling used a technique that allows individual cells and their progeny within a living animal to be followed over time by marking the cells with a new gene. This general approach, known as lineage-tracing, has been a mainstay of classical developmental biology research and has greatly clarified knowledge of tissue stem cells during the last decade.

Their research showed that primordial follicles are highly stable, and that germ-line stem cell activity cannot be detected, even in response to the death of half the existing follicles. The research placed a stringent upper limit on the stem cell activity that could exist in the mouse ovary and escape detectionone stem cell division every two weeks, which is an insignificant level.

What about the rare stem-like cells generated in cultures of ovarian cells? According to Spradling, these cells "likely arise by dedifferentiation in culture," and "the same safety and reliability concerns would apply as to any laboratory-generated cell type that lacks a normal counterpart" in the body.

Explore further: Do ovaries continue to produce eggs during adulthood?

More information: Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles, PNAS, http://www.pnas.org/cgi/doi/10.1073/pnas.1306189110

Researchers have found a way to turn mouse embryonic stem cells into sperm. This finding, reported in the journal Cell in a special online release on August 4th, opens up new avenues for infertility research and treatment. A Kyo ...

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Adults lack stem cells for making new eggs, research shows

Newswise NEW ORLEANS (April 29, 2013) Today, during the 81st American Association of Neurological Surgeons (AANS) Annual Scientific Meeting, researchers announced new findings regarding the development of methods to turn human induced pluripotent stem cells (iPSC) into microglia, which could be used for not only research but potentially in treatments for various diseases of the central nervous system (CNS).

Microglia are the resident inflammatory cells of the CNS and can modulate the outcomes of a wide range of disorders including trauma, infections, stroke, brain tumors, and various degenerative, inflammatory and psychiatric diseases. However, the effective therapeutic use of microglia demonstrated in various animal CNS disease models currently cannot be translated to patients due to the lack of methods for procuring high-purity patient-specific microglia. Developing a method for obtaining these cells would be highly valuable.

In the study Differentiation of Induced Pluripotent Stem Cells to Microglia for Treatment of CNS Diseases, mouse and human iPSCs were generated and sequentially co-cultured on various cell monolayers and in the presence of added growth factors. The microglial identity of the resulting cells was confirmed using fluorescence activated cell sorting analyses, functional assays, gene expression analyses and brain engraftment ability. The study results will be shared by presenting author John K. Park, MD, PhD, FAANS, from 3:34-3:42 p.m. on Monday, April 29. Co-authors are Michael Shen, BS; Yong Choi, PhD; and Hetal Pandya, PhD.

In the results, researchers found mouse and human iPSCs co-cultured with OP9 cells differentiate into hematopoietic progenitor cells (HPCs). HPCs in turn co-cultured with astrocytes, generate cells that express CD11b, Iba-1 and CX3CR1; secrete the cytokines IL-6, IL-1 and TNF-a; generate reactive oxygen species; and phagocytose fluorescent particles, all consistent with a microglial phenotype. Gene expression clustering using self-organizing maps indicates that iPSC-derived microglia more closely resemble normal microglia than other inflammatory cell types. The iPSC-derived microglia engraft and migrate to areas of injury within the brain. These finding have led researchers to conclude that iPSC-derived microglia may one day be useful as gene and protein delivery vehicles to the CNS.

The actual results of our research were not surprising to us, but the overall importance of microglia in a wide variety of brain and spinal cord diseases was surprising. Microglia likely have a role in improving or worsening diseases such as multiple sclerosis, Alzheimers disease, Parkinsons disease, obsessive compulsive disorder and Retts syndrome, just to name a few, said John K. Park, MD, PhD, FAANS. Microglia are the principal immune system cells of the brain and spinal cord, and help fight infections as well as help the healing process after injuries such as trauma and strokes. They also play a poorly understood role in many neurodegenerative and psychiatric diseases. We have developed methods to turn iPSCs into microglia. Because human iPSC can easily be obtained in large numbers, we can now generate large numbers of human microglia not only for use in experiments, but also potentially for use in treatments. The ability to study normal and diseased human microglia will lead to a greater understanding of their roles in healthy brains and various diseases. Diseases that are caused or exacerbated by defective microglia or a paucity of normal microglia may potentially be treated by microglia generated from a patient's iPSC.

Disclosure: The author reported no conflicts of interest.

Media Representatives: The 2013 AANS Annual Meeting Press Kit includes releases on highlighted scientific research, AANS officer and award winners, National Neurosurgery Awareness Week, and other relevant information about this years program. Those releases also will be posted under the Media area on the 2013 AANS Annual Scientific Meeting website (http://www.aans.org/Annual Meeting/2013/Main/Media.aspx). If you would have interest in a topic related to neurosurgery or would like to interview a neurosurgeon either on-site or via telephone during this years event, please contact John Iwanski, AANS Director of Member and Public Outreach, via the onsite press room at (504) 670-4910 or e-mail him at jai@aans.org.

About the 2013 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals%2

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Microglia Can Be Derived From Patient-Specific Human Induced Pluripotent Stem Cells and May Help Modulate the Course ...

Apr. 29, 2013 Mammalian females ovulate periodically over their reproductive lifetimes, placing significant demands on their ovaries for egg production. Whether mammals generate new eggs in adulthood using stem cells has been a source of scientific controversy. If true, these "germ-line stem cells" might allow novel treatments for infertility and other diseases. However, new research from Carnegie's Lei Lei and Allan Spradling demonstrates that adult mice do not use stem cells to produce new eggs.

Their work is published by the Proceedings of the National Academy of Sciences the week of April 29.

Before birth, mouse and human ovaries contain an abundant supply of germ cells, some of which will develop into the eggs that will ultimately be released from follicles during ovulation. Around the time of birth these germ cells have formed a large reserve of primordial follicles -- each containing a single immature egg. Evidence of new follicle production is absent after birth, so it has long been believed that the supply of follicles is fixed at birth and eventually runs out, leading to menopause.

During the last decade, some researchers have claimed that primordial follicles in adult mouse ovaries turn over and that females use adult germ-line stem cells to constantly resupply the follicle pool and sustain ovulation. These claims were based on subjective observations of ovarian tissue and on the behavior of extremely rare ovarian cells following extensive growth in tissue culture, a procedure that is capable of "reprogramming" cells.

Lei and Spradling used a technique that allows individual cells and their progeny within a living animal to be followed over time by marking the cells with a new gene. This general approach, known as lineage-tracing, has been a mainstay of classical developmental biology research and has greatly clarified knowledge of tissue stem cells during the last decade.

Their research showed that primordial follicles are highly stable, and that germ-line stem cell activity cannot be detected, even in response to the death of half the existing follicles. The research placed a stringent upper limit on the stem cell activity that could exist in the mouse ovary and escape detection--one stem cell division every two weeks, which is an insignificant level.

What about the rare stem-like cells generated in cultures of ovarian cells? According to Spradling, these cells "likely arise by dedifferentiation in culture," and "the same safety and reliability concerns would apply as to any laboratory-generated cell type that lacks a normal counterpart" in the body.

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Adults lack stem cells for making new eggs