Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nomadic outposts of transplanted stem cells tracked in Stanford study

16.12.2003


Doctors regularly inject stem cells into patients whose bone marrow has been destroyed by chemotherapy or radiation, but they haven’t known where these cells go after being injected. Research at the Stanford University School of Medicine has yielded an unexpected answer: when injected into mice, these cells may set up camp in one tissue early on but then move to another location or disappear entirely.



Published in the Dec. 15 online edition of the Proceedings of the National Academies of Science, the work upsets current thinking that transplanted stem cells find a habitable niche, settle in for the long haul and begin producing new blood cells. Instead, the newly transplanted cells drift throughout the body, nestling in one of a few homes where their populations subsequently wax and wane until some finally flourish.

Researchers said the procedure used to follow the injected cells’ movements could one day help scientists hone their techniques for transplanting bone-marrow stem cells in humans and optimize therapies for cancer and immunodeficiencies. Developing these types of new stem cell-based treatments for cancer is among the primary goals of Stanford’s Institute for Cancer/Stem Cell Biology and Medicine.


Yu-An Cao, PhD, a research associate and first author of the paper, said that until now injecting bone-marrow stem cells into a patient was like injecting them into a black box. "We didn’t know where those cells were going," he said. Watching the fates of these cells after transplantation had raised more questions than it answered. He said in testing a new protocol, they now can watch to see whether the cells proliferate more quickly or if the patterns of inhabitation are altered.

"We are really curious about what is happening," Cao said. "We want to know why the process is so dynamic with unpredictable fates for the initial stem cell foci. There’s no obvious reason for the stem cells to leave what appears to be a perfectly good place to homestead and proliferate."

Eventually, the work also could help guide transplantation procedures using other types of stem cells. Cao said an upcoming experiment will use the same technique to monitor transplanted neuronal stem cells. "We can monitor the fate of those stem cells and help evaluate transplantation protocols," he said. This type of approach could speed the development of stem cell transplantation therapies for disorders such as Parkinson’s disease.

Cao and Christopher Contag, PhD, assistant professor of pediatrics, radiology, microbiology and immunology, and lead author of the paper, were able to follow the transplanted cells’ travels because they all made a firefly protein called luciferase. This protein produces a dim light when it comes in contact with another molecule called luciferin. Unlike fireflies, mice don’t normally make luciferin, but the recipient mice received doses of the molecule throughout the experiment. Once injected into the recipient mice - whose bone marrow had been destroyed by radiation - the luciferase-producing transplanted cells produced a faint glow. Like a campfire at a new settlement, this dim light pinpointed the cells’ location.

Although the light from luciferase isn’t bright enough to see by eye, an ultrasensitive video camera originally developed by Contag can detect the faint light and show researchers where the glowing cells have settled. The experiment highlighted a handful of stem cell resting places, including the spleen and the bone marrow in the vertebrae, thighbone, shinbone, skull, ribs and sternum, where stem cells were already known to produce new blood cells.

Of all the locations, the spleen and the vertebrae were the two most likely sites for the new cells to settle. These are also the two roomiest compartments, according to Contag. "Where the cells go initially seems to relate to the size of the compartment and its openness," he said. If that location contained existing stem cells, the transplanted stem cell would detect signals indicating, "this compartment is full, we don’t want you here," he added. An empty compartment probably lacks these unwelcoming signals. "The cell knows there’s an empty seat to jump into, and now we can watch them play musical chairs - we just don’t hear the music yet."

What surprised the researchers is how much the pattern varied. In many cases one location would initially house a healthy population of glowing stem cells, only to have that population fade over time while daughter cells set up camp at a distant location. In other mice, locations that initially contained a languishing population of cells would suddenly flourish. When the researchers took stem cells from sites within one transplanted animal and put them into a second mouse lacking bone marrow, those stem cells once again seemed to take a random path to new niches and started the game of musical chairs over again. "This shows that the niche preferences aren’t programmed into the cells," Contag said.

Other Stanford researchers who contributed the work include postdoctoral scholars Amy Wagers, PhD, and Andreas Beilhack, PhD; technician Joan Dusich; research associate Michael Bachmann, MD, DSc; Robert Negrin, MD, associate professor of medicine; and Irving Weissman, MD, the Karel and Avice Beekhuis Professor of Cancer Biology and director of Stanford’s Institute for Cancer/Stem Cell Biology and Medicine.

Contag is one of the founders of Xenogen, which makes the sensitive video camera used in this study.


Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children’s Hospital at Stanford. For more information, please visit the Web site of the medical center’s Office of Communication & Public Affairs at http://mednews.stanford.edu.

PRINT MEDIA CONTACT: Mitzi Baker at 650-725-2106 (mitzibaker@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at 650-723-6912 (mamalone@stanford.edu)

Mitzi Baker | EurekAlert!
Further information:
http://mednews.stanford.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

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...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

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...

Im Focus: Deep inside Galaxy M87

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...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

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...

Im Focus: Microprocessors based on a layer of just three atoms

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>