Carnegie Mellon University biologists have developed an MRI-based technique that allows researchers to non-invasively follow neural stem cells in vivo.
The recently patented technology could be used to further the study of neural stem cells and inform the development of new treatments for brain injury caused by trauma, stroke, Parkinson’s disease and other neurological disorders. The findings, authored by Associate Professor of Biological Sciences Eric Ahrens and Biological Sciences postdoctoral student Bistra Iordanova, are published online in the journal NeuroImage.
Legend had it that once a brain cell dies, it’s lost forever. Neuroscientists now know that this is purely myth, having proved that the brain is constantly producing new neurons. These neural stem cells are born deep in an area of the brain called the subventricular zone. As time goes on, the cells, also called neuroblasts, make their way to other areas of the brain where they mature into functioning neurons. The brain’s ability to regenerate its cells is of great interest to scientists.
“If we could better understand the molecular migratory signals that guide neuroblasts, we could try to redirect these cells to areas of the brain harmed by stroke or traumatic brain injury. With this information, scientists might be able to one day repair the brain,” said Ahrens, who also is a member of the Pittsburgh NMR Center for Biomedical Research.
Studying cells in a living brain is problematic. Common forms of in vivo cell imaging like fluorescence and bioluminescence rely on light to produce images, making them unsuitable for viewing neuroblasts buried deep beneath the skull and layers of opaque tissue. Until now, scientists had only been able to study neuronal stem cells by looking at slices of the brain under a microscope. Ahrens was able to surmount this problem using MRI technology.
Rather than light, MRI uses magnets to create high-resolution images. A typical MRI scan uses a magnetic field and radio frequency pulses to cause the hydrogen protons found in the body’s water molecules to give off signals. Those signals are converted into a high-resolution image.
At the foundation of this work is a technology Ahrens developed. As reported in a 2005 issue of Nature Medicine, Ahrens developed a method that causes cells to produce their own contrast agent allowing them to be imaged with MRI. Using a viral vector, Ahrens incorporated the gene that produces the naturally occurring metalloprotein ferritin into living cells. Ferritin, which is present in all biological cells, harvests and stores naturally occurring iron. When the cells tagged with ferritin began to produce increased amounts of the protein, they draw in additional iron, turning themselves into nanomagnets. This disrupts the magnetic field surrounding the tagged cells, changing the signal given off by adjacent water molecules. This change appears as dark spots on the MRI image indicating the cells' presence. Since then, Ahrens’ team has improved on the process, developing an engineered form of ferritin that is a more effective MRI reporter than naturally occurring ferritin.
In the current study, Iordanova and Ahrens used the same technique as in the initial study, this time tagging neuroblasts with the engineered ferritin. They incorporated the DNA sequence for the engineered metalloprotein into an adenovirus vector, which they then injected into the subventricular zone of a rat brain. The adenovirus infected the neural stem cells giving the cells the genetic instructions to begin producing the ferritin reporter. Iordanova then imaged the brain with MRI and found that she was able to follow — in real time — the neuroblasts as they traveled toward the olfactory bulb and ultimately formed new inhibitory neurons. These results mirrored what had been observed in histology studies.
Recently, Carnegie Mellon received a patent for the reporter. Ahrens hopes to continue to develop the technology in order to allow researchers to better understand neuronal stem cells and how neurons regenerate. Ahrens also plans to use the reporters to improve clinical trials of cell-based therapies. By incorporating the reporter into the cells before implantation, researchers would be able to find the answer to a number of critical questions.
“Where do these cells go, days, weeks and months later? How do we know that they’ve grafted to the right cells? Or have they grafted in the wrong place? Or died?” Ahrens asked. “The reporter can show us the answers.”
The National Science Foundation and National Institutes of Health funded this research.
About Carnegie Mellon: Carnegie Mellon (www.cmu.edu) is a private, internationally ranked research university with programs in areas ranging from science, technology and business, to public policy, the humanities and the fine arts. More than 11,000 students in the university’s seven schools and colleges benefit from a small student-to-faculty ratio and an education characterized by its focus on creating and implementing solutions for real problems, interdisciplinary collaboration and innovation. A global university, Carnegie Mellon’s main campus in the United States is in Pittsburgh, Pa. It has campuses in California’s Silicon Valley and Qatar, and programs in Asia, Australia, Europe and Mexico. The university is in the midst of a $1 billion fundraising campaign, titled “Inspire Innovation: The Campaign for Carnegie Mellon University,” which aims to build its endowment, support faculty, students and innovative research, and enhance the physical campus with equipment and facility improvements.
By: Jocelyn Duffy, email@example.com, 412-268-9982
Jocelyn Duffy | EurekAlert!
Closing the carbon loop
08.12.2016 | University of Pittsburgh
Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
08.12.2016 | Life Sciences
08.12.2016 | Physics and Astronomy
08.12.2016 | Materials Sciences