Functional mouse eggs made from artificial stem cells
Dr Katie Howe
Progress Educational Trust
26 October 2016
Scientists in Japan are the first to have created live mouse pups from eggs that were made from stem cells.
It is the first time that the entire process of egg development has been recreated in vitro. If the technique could be applied to humans, it could be used to treat female infertility – for older women and those whose ovaries have been damaged by cancer treatment.
'From a technical point of view it could work,' said study lead author Dr Katsuhiko Hayashi from Kyushu University. 'If we could make human eggs, it could be a very powerful tool for curing infertility.'
The study, which was published in Nature, describes how the researchers first created immature eggs by reprogramming two different types of stem cells: embryonic stem cells and induced pluripotent stem cells (iPS cells), which were produced by transforming skin cells from the tails of female mice.
The immature eggs were then matured in a dish before being fertilised using IVF and transferred into female mice. The procedure created 4048 mature eggs, from which 1348 embryos were made. Eventually, 11 healthy pups were born, eight of which were from the skin-derived iPS cells.
The study builds on previous research in which Dr Hayashi and colleagues created immature mouse eggs from iPS cells. However, those eggs needed to fully mature within the ovaries of living mice.
In the new study, immature eggs were cultured in a dish alongside ovarian cells taken from mouse fetuses, which encouraged them to mature. Dr Hayashi's team are now trying to develop an artificial reagent that could replace the ovarian tissue in the protocol.
Although promising, the process is currently very inefficient and has a very high failure rate. Just 3.5 percent of embryos created from in vitro matured artificial eggs led to live births, compared with 62 percent of embryos created from eggs matured inside the mouse. The artificially created eggs also had unusual patterns of gene expression, suggesting that the resulting pups may have developmental abnormalities, even though they appeared healthy and were fertile.
Dr Hayashi next intends to attempt this process in a non-human primate, which will be much more complicated. If the same procedure is eventually be replicated in humans, it could potentially be used to make artificial eggs from male skin cells, raising the possibility of creating babies with two genetic fathers. However, so far Dr Hayashi's team have not been successful when using male skin cells.
The technology also raises many ethical questions that will need to be discussed. Professor Azim Surani, a stem cell scientist at the Gurdon Institute of the University of Cambridge, who was not involved in the study, said: 'This is the right time to involve the wider public in these discussions, long before and in case the procedure becomes feasible in humans.'
SOURCES & REFERENCES
Eggs made from skin cells in lab could herald end of infertility
New Scientist | 17 October 2016
Healthy Baby Mice Produced from Mouse Mom's Skin Cells
Scientific American | 17 October 2016
Healthy mice born from first lab-grown eggs spark calls for debate on future use
The Guardian | 17 October 2016
Mouse eggs made from skin cells in a dish
Nature News | 17 October 2016
Reconstitution in vitro of the entire cycle of the mouse female germline
Nature | 17 October 2016
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Reproduced with permission from BioNews, an email and online sources of news, information and comment on assisted reproduction and genetics.
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12 November 2016
Fact Sheet 2. Re: Not Suitability To Use Artificially Created, Modified Or Reprogrammed Human Eggs (Or Sperm) To Produce Babies
The artificially created, modified or reprogrammed human eggs (or sperm) include: human eggs (or sperm) produced by the techniques (or procedures) with human cloning, organ cloning, tissue cloning, embryonic stem cells, adult stem cells, induced pluripotent stem cells, egg stem cells and other germline stem cells, etc.
1. Dolly, the first animal of reprogrammed live birth, suffered from many kinds of diseases and with shorter life, which was the result of Somatic Cell Nuclear Transfer or called animal cloning (rather than germ cell nuclear transfer- performed by Dr. John Zhang, which was not reprogrammed and was not called cloning, and which was banned by FDA in year 2000).
2. All of the artificial sperm and eggs created from reprogrammed stem cells in human and animal research in recent 10 years showed abnormal functions although with normal morphology.
3. No one in the world, recently or in foreseeable future, can correctly and thoroughly reprogram stem cells (late totipotent and pluripotent stem cells) and differentiated cells back to be the normal germ cells (eggs or sperm). The reason are:
A. Reprogram is the reverse course of cell and tissue differentiating course. Thus reprogram is much more difficult than the differentiation of stem cells. (The example: a boat runs easier with stream and runs more difficult against stream.)
B. The activation reagents which are used in reprogram the cells are toxic to after-birth human, and they are more toxic in germ cells to be reprogarmmed.
C. To thoroughly and correctly reprogram a (late totipotent, pluripotent or differentiated) cell to be a normal egg cell will need to perform correct and thorough methylation with correct dosage for all of the locations on every genes which need not to express their genes at the egg stage. At the same time, demethylation should be performed at the correct location of other genes which need to express their genes.
D. To thoroughly and correctly reprogram a cell to be a normal egg cell will need to perform much more difficult work: to remodel all chromatin configuration from the later or differentiated cell stages back to the egg cell stage. It will need to change amino acids to alter the shape of histones, which will need to perform correct and precise acetylation, methylation, ubiquitylation, phosphorylation and sumoylation.
E. Stem cell research, induced pluripotent stem cell (iPSC) research, egg stem cell research and tissue cloning are all using reprogram techniques to achieve their aim, in which tissue cloning techniques are the most thorough reprogram techniques. Even using the best tissue cloning techniques still could not reprogram a later cell stages back to the normal egg cell stage.
F. Now all of the stem cell regrogram techniques are based on genes related to cancer.
4. Any procedures in extraction and purification of germline stem cells or other stem cells will lead to DNA mutation.
5. Any long term in vitro culture, when over 3 to 7 days, will easily produce DNA mutation. If culture in vitro over 2 weeks, the cultured cells will easily produce chromosomal abnormalities. The longer culture time, the more abnormalities will happen. The reasons are:
A. Most of the culture dishes and pipettes are toxic with benzene rings;
B. The air and water quality and concentration are much worse than those in vivo fluid;
C. Any degradation from amino acids, proteins, RNA and DNA will harm normal functions and structures of proteins, RNA and DNA;
D. Any environment and nutrition differ from the in vivo natural conditions will lead to DNA mutation and chromosomal abnormalities.
E. Antibiotics using in the culture media and infectious factors (fungi, bacteria, mycoplasma, and virus, etc.) will lead to abnormal proteins, RNA, DNA and chromosomes.
6. No techniques can restore the telomere length of the stem cell to the normal telomere length in the normal human eggs, which is related the longevity of human life.
7. In vitro meiosis will lead to DNA and chromosomal abnormalities.
8. For the aim to solve patient’s infertile problem, it is not worth changing human being.
This is a part of letter sent to U.S. FDA Director on March 22, 2013, RE: Protect Human beings in Heredity by Ke-Hui Cui, M.D., Ph.D.
Please also read:
1. “HUMAN BEINGS SHOULD NOT BE CHANGED IN HEREDITY” published on ivf.net 18 October 2016 comment for “Mitochondrial replacement therapy and the welfare of the child” response on 02 November 2016.
2. “CHANGING HUMAN BEINGS IN HEREDITY IS MISLEADING AND INFAMOUS” published on ivf.net 01 November 2016 comment for “ ‘Three-person babies’ grow up into healthy teenagers” response on 07 November 2016.