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Blastocyst |
Semos the Rhesus monkey (cell-donor) |
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Blastocyst |
Semos the Rhesus monkey (cell-donor) |
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Nature
advance online publication 14 November 2007 |
doi:10.1038/nature06357; Published online
14 November
2007
J Byrne, D Pedersen, L Clepper, M Nelson, W Sanger, S Gokhale, D Wolf & S Mitalipov
Abstract
Derivation of embryonic stem (ES) cells genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing concerns regarding rejection by the host immune system. However, the concept has only been achieved in the mouse, whereas inefficient reprogramming and poor embryonic development characterizes the results obtained in primates. Here, we used a modified SCNT approach to produce rhesus macaque blastocysts from adult skin fibroblasts, and successfully isolated two ES cell lines from these embryos. DNA analysis confirmed that nuclear DNA was identical to donor somatic cells and that mitochondrial DNA originated from oocytes. Both cell lines exhibited normal ES cell morphology, expressed key stem-cell markers, were transcriptionally similar to control ES cells and differentiated into multiple cell types in vitro and in vivo. Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES cells and demonstrate proof-of-concept for therapeutic cloning in primates.
NEW YORK (AP) — American scientists reported Wednesday that they had cloned embryos from a 9-year-old male monkey and derived stem cells from them, reaching a long-sought goal that may pay off someday in new treatments for people.
The work was published online by the journal Nature, which took the unusual step of asking another team of researchers to verify the work before publication. That reflects the legacy of a spectacular fraud in stem cell research from South Korea several years ago.
The new work is important because someday researchers hope to use such a process in humans to make transplant tissue that’s genetically matched to patients, thus avoiding the risk of rejection.
Scientists had tried for years to produce stem cells through cloning in monkeys, because the animals are so closely related to humans and so provide a good way to study the process. But until now, it hasn’t worked.
The advance is reported by Shoukhrat Mitalipov of the Oregon National Primate Research Center in Portland with colleagues there and elsewhere. Some media outlets, including The Associated Press, had reported their success earlier, based on a presentation at a scientific meeting.
The scientists combined DNA from skin cells of the monkey, a rhesus macaque, with unfertilized monkey eggs that had their own DNA removed. The eggs were grown into early embryos, from which stem cells were removed.
The researchers cautioned that even if their procedure could be used to produce human stem cells, it’s far too inefficient to be used in medicine. Human unfertilized eggs are in short supply and are cumbersome to obtain. The monkey work required 304 eggs from 14 female macaques to produce just two batches of stem cells, they wrote.
Still, Dr. George Daley of the Harvard Stem Cell Institute, who was familiar with the work, told the AP it was a “a very important demonstration” that the process is feasible in primates, the group that includes monkeys and humans.
Nature also published a verification of the results by an Australian team. In an e-mail to the AP, the journal said one reason was the highly publicized 2004 fraud that came out of South Korea, where researchers claimed to have produced stem cells from a cloned human embryo.
The journal emphasized that its request didn’t indicate mistrust of scientists in the cloning field. Instead, the statement said, because of “questions will likely be raised about the veracity of the (American) experiments, given recent history in the cloning field, we view this as a relatively straightforward way of putting these questions to rest.”
The Australian study, by David Cram and others at the Monash University, used DNA analysis of the male macaque, the two monkeys that donated eggs for creating the embryos, and the stem cells. The result “demonstrates beyond any doubt” that the stem cells came from cloned embryos, the Australians wrote in their Nature paper.
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Nature
advance online publication 14 November 2007 |
doi:10.1038/nature06357; Published online
N.B “Semos” is the name of the monkey-deity in the film, Planet of the Apes.
From Dolly to Semos
1996 Birth of Dolly the sheep, above, the first mammal cloned with somatic cell nuclear transfer technique. The achievement was announced in 1997
2002 First cloned cat, Cc or Copy Cat, born. Other animals to be cloned include rats, mice and cows
2002 Raelian cult claims birth of first cloned human baby. Story discounted as fantasy
2004 South Korean team led by Woo Suk Hwang announces first cloned human embryo
2005 Hwang’s team announces further human clones, from which stem cells have been extracted
2005 Scientists at Newcastle University produce cloned human embryo, but it dies before stem cells can be removed
2005 Hwang’s human research shown to have been faked. His papers are withdrawn by the journals that published them
2007 Announcement that US scientists have cloned monkey embryos and extracted stem cells
2017 Chinese Scientists
claim to have successfully cloned a Macaque Monkey
Coverage in
Smithsonian magazine
Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer
Cell January 24, 2018, Liu et al.
Cell, VOLUME 172, ISSUE 4, P881-887.E7, FEBRUARY 08, 2018
Published: January 24, 2018 DOI:https://doi.org/10.1016/j.cell.2018.01.020
Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang, Yuting Xu, Xiaotong Zhang, Yong Lu, Zhanyang Wang, Muming Poo, Qiang Sun
Highlights
• Somatic cell nuclear transfer (SCNT) using fetal fibroblasts yielded two live monkeys
• Epigenetic modulators promoted development and pregnancy rate of SCNT embryos
• SCNT using adult cumulus cells yielded live births of monkeys that were short-lived
• Genetic analysis confirmed the clonal origin of the SCNT monkey offspring
Summary
Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys ( Macaca fascicularis) by somatic cell nuclear transfer (SCNT).
We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys.
For SCNT using fetal monkey fibroblasts,
6 pregnancies were confirmed
in 21 surrogates
and yielded 2 healthy babies.
For SCNT using adult monkey cumulus cells,
22 pregnancies were confirmed
in 42 surrogates
and yielded 2 babies that were short-lived.
In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts.
