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!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy