Researchers from the Massachusetts General Hospital Center for Regenerative Medicine (MGH-CRM) and the Harvard Stem Cell Institute have a developed a new type of human pluripotent stem cell that can be manipulated more readily than currently available stem cells. As described in the June 4 Cell Stem Cell, these new cells could be used to create better cellular models of disease processes and eventually may permit repair of disease-associated gene mutations.
"It has been fairly easy to manipulate stem cells from mice, but this has not been the case for traditional human stem cells," explains Niels Geijsen, PhD, of the MGH-CRM, who led the study. "We had previously found that the growth factors in which mouse stem cells are derived define what those cells can do, and now we've applied those findings to human stem cells."
The first mammalian embryonic stem cells (ESCs) were derived from mice and have proven very useful for studying gene function and the impact of changes to individual genes. But techniques used in these studies to introduce a different version of a single gene or inactivate a particular gene were ineffective in human ESCs. In addition, human ESCs proliferate much more slowly than do cells derived from mice and grow in flat, two-dimensional colonies, while mouse ESCs form tight, three-dimensional colonies. It is been extremely difficult to propagate human ESCs from a single cell, which prevents the creation of genetically manipulated human embryonic stem cell lines.
In previous work, Geijsen and his colleagues demonstrated that the growth factor conditions under which stem cells are maintained in culture play an important role in defining the cells' functional properties. Since the growth factors appeared to make such a difference, the researchers tried to make a more useful human pluripotent cell using a new approach. They derived human induced pluripotent stem cells (iPSCs) – which are created by reprogramming adult cells and have many of the characteristics of human ECSs, including resistance to manipulation – in cultures containing the growth factor LIF, which is used in the creation of mouse ESCs.
The resulting cells visibly resembled mouse ESCs and proved amenable to a standard gene manipulation technique that exchanges matching sequences of DNA, allowing the targeted deactivation or correction of a specific gene. The ability to manipulate these new cells depended on both the continued presence of LIF and expression of the five genes that are used in reprogramming adult cells into iPSCs. If any of those factors was removed, these hLR5- (for human LIF and five reprogramming factors) iPSCs reverted to standard iPSCs.
"Genetic changes introduced into hLR5-iPSCs would be retained when they are coverted back to iPSCs, which we then can use to generate cell lines for future research, drug development and someday stem-cell based gene-correction therapies," says Geijsen. He is an assistant professor of Medicine at Harvard Medical School and a principal faculty member of the Harvard Stem Cell Institute.
Co-authors of the Cell Stem Cell paper are lead author Christa Buecker, MGH-CRM and Harvard Stem Cell Institute (HSCI); Hsu-Hsin Chen, PhD, Laurence Dahern, and Konrad Hochedlinger, PhD, MGH-CRM and HSCI; Patricia Okwieka, MGH-CRM; Jose Polo, PhD, MGH Cancer Center; Lei Bu, PhD, MGH Cardiovascular Research Center; Tahsin Stefan Barakat and Joost Gribnau, PhD, University Medical Center, Rotterdam, The Netherlands; and Andrew Porter, PhD, Imperial College London, U.K. The study was supported by grants from the National Institutes of Health, the Dutch Science Organization, the Gottlieb Daimler and Karl Benz Foundation and the National Science Council of Taiwan.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News