Future medicine: Stem cells can leverage silica nanoparticles to track where they actually go

QDOTS imagesCAKXSY1K 8Giving patients stem cells packaged with silica nanoparticles could help  doctors determine the effectiveness of the treatments by revealing where the  cells go after they’ve left the injection needle.

Researchers from Stanford University report in a paper  published on Wednesday in the journal Science Translational Medicine  that silica nanoparticles taken up by stem cells make the cells visible on  ultrasound imaging. While other imaging techniques such as MRI can show where  stem cells are located in the body, that method is not as fast, affordable, or  widely available as an ultrasound scanner, and more importantly, it does not  offer a real-time view of injection, say experts.

Stem cells have significant medical promise because they can be turned into  other types of living cell. As well as helping doctors adjust therapeutic  dosages in patients, the new technique could help scientists perfect stem cell  treatments, says senior author Sanjiv  Gambhir. “For the most part, researchers shoot blindly—they don’t quite know  where the cells are going when they are injected, they don’t know if they home  in to the right target tissue, they don’t know if they survive, and they don’t  know if they leak into other tissue types,” says Gambhir.

This, in part, could be slowing advances in stem cell treatments. “If stem  cells are going to be used as a legitimate medical treatment for the repair of  damaged or diseased tissue, then we will need to know precisely where they are  going so the treatments can be optimized,” says Lara  Bogart, a physicist at the University of Liverpool. Bogart is developing  magnetic nanoparticles for tracking stem cells using MRI.To get a better view of where cells are going during and after injection,  Gambhir and colleagues used nanoparticles made of silica, a material that  reflects sound waves, so it can be detected in an ultrasound scan. The  nanoparticles were incubated with mesenchymal stem cells, which can develop into  cell types including bone cells, fat cells, and heart cells. The cells ingested  the nanoparticles, which did not change the cells’ growth rate or ability to  develop into different cell types. Inside the cells, the nanoparticles clumped  together, which made them more visible in an ultrasound.

The researchers then injected the nanoparticle-laden stem cells into the  hearts of mice and tracked their movements. Many research groups are testing  stem cells as a treatment after a heart attack or for other heart conditions in  both lab animals (see “A  Step Toward Healing Broken Hearts with Stem Cells” and “Injecting  Stem Cells into the Heart Could Stop Chronic Chest Pain”) as well as in  patients in clinical trials. A fast and real-time imaging tool could help  because researchers and doctors need to be sure that the cells reach the most  beneficial spots in a sickly heart.

“It’s very important to know where you inject the cells because you don’t  want to put them in areas damaged by the heart attack; that tissue is dead and a  very hostile environment,” says Jeff Bulte, a cell engineer at the Johns Hopkins  University School of Medicine who was not involved in the study. “On the other  hand, you want to place them as close to the site of damage as possible,” he  says.

The silica nanoparticles can also be detected in MRI machines because they  contain a strongly magnetic heavy metal known as gadolinium that shows up in the  scans. And they can be detected optically (through microscopes) because they  carry a fluorescent dye. “This gives us three complementary ways to image the  same particle,” says Bogart. Depending on the part of the body receiving the  transplant, the type of scanner available and the amount of time since  injection, a researcher may choose one method over another.

The mice used in the study were healthy, but the team plans to test the  tracking method in mice or other lab animals that have heart damage. The team  will also use the nanoparticles in different cell types and do more toxicity  studies prior to filing for FDA approval to test the nanoparticles in humans. “It will be about a three-year process to do first-in-man studies,” says  Gambhir.

Read more: http://medcitynews.com/2013/03/future-medicine-stem-cells-can-leverage-silica-nanoparticles-to-track-cells-once-in-the-body/#ixzz2OXjcfbXH


Researchers can deliver RNA, proteins and nanoparticles for many applications

QDOTS imagesCAKXSY1K 8How to squeeze large molecules into cells

By deforming cells, researchers can deliver RNA, proteins and nanoparticles for many applications
January 28, 2013

As cells squeeze through a narrow channel, tiny holes open in their membranes, allowing large molecules such as RNA to pass through (credit: Armon Sharei and Emily Jackson)

Living cells are surrounded by a membrane that tightly regulates what gets in and out of the cell. This barrier is necessary for cells to control their internal environment, but it makes it more difficult for scientists to deliver large molecules such as nanoparticles for imaging, or proteins that can reprogram them into pluripotent stem cells.squeezed_cells

Researchers from MIT have now found a safe and efficient way to get large molecules through the cell membrane, by squeezing the cells through a narrow constriction that opens up tiny, temporary holes in the membrane. Any large molecules floating outside the cell — such as RNA, proteins or nanoparticles — can slide through the membrane during this disruption.

Using this technique, the researchers were able to deliver reprogramming proteins and generate induced pluripotent stem cells with a success rate 10 to 100 times better than any existing method. They also used it to deliver nanoparticles, including carbon nanotubes and quantum dots, which can be used to image cells and monitor what’s happening inside them.

“It’s very useful to be able to get large molecules into cells. We thought it might be interesting if you could have a relatively simple system that could deliver many different compounds,” says Klavs Jensen, the Warren K. Lewis Professor of Chemical Engineering, professor of materials science and engineering, and a senior author of a paper describing the new device in the Proceedings of the National Academy of Sciences.

Robert Langer, the David H. Koch Institute Professor at MIT, is also a senior author of the paper. Lead authors are chemical engineering graduate student Armon Sharei, Koch Institute research scientist Janet Zoldan, and chemical engineering research associate Andrea Adamo.

The new MIT system appears to work for many cell types — so far, the researchers have successfully tested it with more than a dozen types, including both human and mouse cells. It also works in cells taken directly from human patients, which are usually much more difficult to manipulate than human cell lines grown specifically for lab research.

The new device builds on previous work by Jensen and Langer’s labs, in which they used microinjection to force large molecules into cells as they flowed through a microfluidic device. This wasn’t as fast as the researchers would have liked, but during these studies, they discovered that when a cell is squeezed through a narrow tube, small holes open in the cell membrane, allowing nearby molecules to diffuse into the cell.

To take advantage of that, the researchers built rectangular microfluidic chips, about the size of a quarter, with 40 to 70 parallel channels. Cells are suspended in a solution with the material to be delivered and flowed through the channel at high speed — about one meter per second. Halfway through the channel, the cells pass through a constriction about 30 to 80 percent smaller than the cells’ diameter. The cells don’t suffer any irreparable damage, and they maintain their normal functions after the treatment.

Special delivery

The research team is now further pursuing stem cell manipulation, which holds promise for treating a wide range of diseases. They have already shown that they can transform human fibroblast cells into pluripotent stem cells, and now plan to start working on delivering the proteins needed to differentiate stem cells into specialized tissues.

Another promising application is delivering quantum dots — nanoparticles made of semiconducting metals that fluoresce. These dots hold promise for labeling individual proteins or other molecules inside cells, but scientists have had trouble getting them through the cell membrane without getting trapped in endosomes.

In a paper published in November, working with MIT graduate student Jungmin Lee and chemistry professor Moungi Bawendi, the researchers showed that they could get quantum dots inside human cells grown in the lab, without the particles becoming confined in endosomes or clumping together. They are now working on getting the dots to tag specific proteins inside the cells.

The researchers are also exploring the possibility of using the new system for vaccination. In theory, scientists could remove immune cells from a patient, run them through the microfluidic device and expose them to a viral protein, and then put them back in the patient. Once inside, the cells could provoke an immune response that would confer immunity against the target viral protein.

The research was funded by the National Institutes of Health and the National Cancer Institute.