Researchers at Children's Hospital Boston report a new and efficient strategy, using eggs alone, for creating mouse embryonic stem cells that can be transplanted without the risk of rejection because the cells are compatible with the recipient's immune system. The findings will be published online in the journal Science on December 14.
Though done in mice, the work establishes the principle of using unfertilized eggs as a source of customized embryonic stem cells that are genetically matched to the egg donor at the genes that control recognition of cells by the immune system, making them potentially useful for transplantation therapies. There are several caveats, including the fact that only females could benefit from this technique, donating their own eggs to generate the stem cells, and concerns that the tissues derived from this special type of embryonic stem cells might not function normally.
"This technique, if proven effective in humans, offers an efficient way of generating customized stem cell lines from women," says George Q. Daley, MD, PhD, senior author on the paper, who is the Associate Director of the Children's Hospital Boston Stem Cell Program and a member of the Executive Committee of the Harvard Stem Cell Institute. "It would eliminate tissue matching and tissue rejection problems, a major obstacle to successful tissue transplantation."
Embryonic stem cells are "master cells" that can generate all tissue types in the body. In 2002, Daley's laboratory collaborated with the laboratory of Rudolf Jaenisch, PhD, of the Whitehead Institute, MIT to demonstrate the first use of another method, somatic cell nuclear transfer, to create customized embryonic stem cells to repair genetic defects in mice. But somatic cell nuclear transfer (sometimes called therapeutic cloning) is a technically demanding and inefficient process that involves transferring the nucleus of a donor cell into an egg from which the nucleus has been removed.
"We will not stop testing nuclear transfer, because it is the only means we know for generating embryonic stem cells that are genetically identical to a patient," says Daley, who heads one of two Harvard Stem Cell Institute-associated labs attempting to create human embryonic stem cells with that technique. "However, generating embryonic stem cells from unfertilized eggs is far more efficient than nuclear transfer, and therefore may allow us to move toward human applications sooner."
In the new study, Daley, first author Kitai Kim, PhD, and colleagues at Harvard Medical School, Brigham and Women's Hospital and Massachusetts General Hospital used unfertilized eggs of mice to create so-called parthenogenetic embryonic stem cells. Parthenogenesis is a method of reproduction, common in plants and in some animals, in which the female can generate offspring without the contribution of a male. It doesn't normally occur in mice, but Daley, Kim and colleagues were able to induce unfertilized mouse eggs to develop through a series of chemical treatments, then generated embryonic stem cells.
Next, they used genetic typing to identify those embryonic stem cells that shared with the egg donor the genes responsible for tissue matching, called the major histocompatibility complex (MHC). When they injected these selected embryonic stem cells into MHC-matched mice, a variety of specialized tissues formed, with no rejection and no need to suppress the recipients' immune system.
Daley's laboratory at Children's Hospital Boston is now trying to replicate its results with human eggs.
As Daley noted, there are several potential limitations to embryonic stem cells generated by parthenogenesis. First, since parthenogenetic embryonic stem cells are made from eggs, the technique is only applicable to females. (Methods exist for deriving embryonic stem cells using sperm from men, but these techniques are as technically challenging and inefficient as somatic cell nuclear transfer, Daley says.)
There are also potential safety concerns. Embryonic stem cells created through parthenogenesis have altered expression of certain genes that are "imprinted." Imprinted genes are marked for expression in a special way based on whether they are passed to offspring by the egg or the sperm. Because parthenogenetic embryonic stem cells are made from eggs only, they carry no paternally imprinted genes, and instead carry two copies of maternally imprinted genes. Altered expression of imprinted genes has been linked with cancer and poor growth in some tissues. In addition, embryonic stem cells created through parthenogenesis may have some regions of their genome that contain duplicated copies of mutant genes that have been linked with malignancies or abnormal tissue growth.
"Right now this technique is useful for basic research, but we are hopeful that parthenogenetic cells might prove useful for therapies," Daley says. "Our cells produce normal tissues in mice, and there is a report in the clinical literature of a human patient whose blood was derived entirely from parthenogenetic cells. However, we'll have to demonstrate the safety and durability of cells derived from parthenogenetic embryonic stem cells before we could imagine any clinical use."
Anna Gonski | EurekAlert!
Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo
Full of hot air and proud of it
18.04.2018 | University of Pittsburgh
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy