Pluripotent stem cells can turn, or differentiate, into any cell type in the body, such as nerve, muscle or bone, but inevitably some of these stem cells fail to differentiate and end up mixed in with their newly differentiated daughter cells.
Because these remaining pluripotent stem cells can subsequently develop into unintended cell types — bone cells among blood, for instance — or form tumors known as teratomas, identifying and separating them from their differentiated progeny is of utmost importance in keeping stem cell–based therapeutics safe.
Now, UCLA scientists have discovered a new agent that may be useful in strategies to remove these cells. Their research was published online April 15 in the journal Developmental Cell and will appear in an upcoming print edition of the journal.
The study was led by Carla Koehler, a professor of chemistry and biochemistry at UCLA, and Dr. Michael Teitell, a UCLA professor of pathology and pediatrics. Both are members of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA and UCLA's Jonsson Comprehensive Cancer Center.
In work using the single-celled microorganism known as baker's yeast, or Saccharomyces cerevisiae, as a model system, Koehler, Teitell and their colleagues had discovered a molecule called MitoBloCK-6, which inhibits the assembly of cells' mitochondria — the energy-producing "power plants" that drive most cell functions. The research team then tested the molecule in a more complex model organism, the zebrafish, and demonstrated that MitoBloCK-6 blocked cardiac development.
However, when the scientists introduced MitoBloCK-6 to differentiated cell lines, which are typically cultured in the lab, they found that the molecule had no effect at all. UCLA postdoctoral fellow Deepa Dabir tested the compound on many differentiated lines, but the results were always the same: The cells remained healthy.
"I was puzzled by this result, because we thought this pathway was essential for all cells, regardless of differentiation state," Koehler said.
The team then decided to test MitoBloCK-6 on human pluripotent stem cells. Postdoctoral fellow Kiyoko Setoguchi showed that MitoBloCK-6 caused the pluripotent stem cells to die by triggering apoptosis, a process of programmed cell suicide.
Because the tissue-specific daughter cells became resistant to death shortly after their differentiation, the destruction of the pluripotent stem cells left a population of only the differentiated cells. Why this happens is still unclear, but the researchers said that this ability to separate the two cell populations could potentially reduce the risk of teratomas and other problems in regenerative medicine treatment strategies.
"We discovered that pluripotent stem cell mitochondria undergo a change during differentiation into tissue-specific daughter cells, which could be the key to the survival of the differentiated cells when the samples are exposed to MitoBloCK-6," Teitell said. "We are still investigating this process in mitochondria, but we now know that mitochondria have an important role in controlling pluripotent stem cell survival."
MitoBloCK-6 is what is known as a "small molecule," which can easily cross cell membranes to reach mitochondria. This quality makes MitoBloCK-6 — or a derivative compound with similar properties — ideal for potential use as a drug, because it can function in many cell types and species and can alter the function of mitochondria in the body for therapeutic effects.
"It is exciting that our research in the one-cell model baker's yeast yielded an agent for investigating and controlling mitochondrial function in human pluripotent stem cells," Koehler said. "This illustrates that mitochondrial function is highly conserved across organisms and confirms that focused studies in model systems provide insight into human stem-cell biology. When we started these experiments, we did not predict that we would be investigating and controlling mitochondrial function in pluripotent stem cells."
The research was supported by the California Institute for Regenerative Medicine, the National Institutes of Health, the United Mitochondrial Disease Foundation, and the Development and Promotion of Science and Technology Talents Project of the Royal Thai Government.
The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: UCLA's stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Broad Stem Cell Research Center is committed to a multidisciplinary, integrated collaboration among scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed toward future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine at UCLA, UCLA's Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2012, the Jonsson Cancer Center was once again named among the nation's top 10 cancer centers by U.S. News & World Report, a ranking it has held for 12 of the past 13 years.
For more news, visit the UCLA Newsroom and follow us on Twitter.
Shaun Mason | EurekAlert!
Further reports about: > Cancer > Comprehensive Cancer Center > MitoBloCK-6 > Regenerative Therapien > Stem cell innovation > UCLA > cell death > cell type > clinical application > daughter cells > embryonic stem cell > mitochondrial function > pluripotent stem > pluripotent stem cells > power plant > stem cells
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences