Stem Cells to Cure Disease

By Stephanie Smith

BU News Service


Despite the great debate over bioethical issues, stem cell research continues. Now, Boston-based researchers think they have hit upon a major development in stem cell studies, one which could benefit a large populations of patients suffering from inflammatory diseases.

A group of researchers from Brigham and Women’s Hospital, the Harvard Stem Cell Institute, MIT, and Massachusetts General Hospital have uncovered a way for adult stem cells to act as a “drug factory” at the site of inflammation in the body.

Speaking to the Harvard Stem Cell Institute, researcher Jeffrey Karp said, “If you think of a cell as a drug factory, what we’re doing is targeting cell-based, drug factories to damaged or diseased tissues, where the cells can produce drugs at high enough levels to have a therapeutic effect.”


A graphic depiction of the cells acting as a drug factory to suppress the inflammation.
A graphic depiction of the cells acting as a drug factory to suppress the inflammation.

Lead author Oren Levy, PhD was cautiously optimistic about the discovery’s potential to treat certain diseases associated with inflammation, such as heart attack, multiple sclerosis, and even certain types of cancer.

“It’s important to not create false hope, but we do see a lot of progress to be made,” Levy said.

Levy, started the research venture to test his hypothesis that stem cells could be used to target a localized region of the body. The study, published on Aug. 21 in the scientific journal Blood, also included study authors Jeffrey Karp, Weian Zhao, Mehmet Fatih Yanik, and Charles Lin.

Stem cells are undifferentiated cells – essentially cells that haven’t decided yet if they will become a blood cell, or a skin cell or any other kind of specialized cell. At the “stem cell” phase, these cells still have the potential to turn into any specialized cell. This study used adult stem cells, which are less controversial than embryonic stem cells only found in embryos that have not fully developed.

Researchers tweaked these adult stem cells using modified strands of mRNA, a type of single stranded genetic material similar to DNA that is naturally found in human cells. Upon mRNA insertion, the cells produced an anti-inflammatory protein, known as interleukin-10.

These modified human stem cells were injected into the bloodstream of a mouse with inflammation in the ear. The cells targeted the site of inflammation and released the interleukin-10 to reduce the swelling.

“We basically used the cells as a vehicle to deliver, and they did,” Levy said in prepared remarks.

Ultimately, the group was able to develop a type of cell that has the capability of reaching the site of inflammation and suppressing  it.

“If you think about biological therapeutic drugs, they’re a huge part of medicine, but there [are] still challenges,” he adds. “It’s hard to target them where you want them to act.”

Though this study looked at a simple local inflammation model in the ear of a mouse, the group hopes to target a clinically relevant model in the future for common conditions like inflammation in the wrists caused by arthritis. But, Levy warns, “This has a lot of potential happening in the next years to come, but it’s still early.”

This research garnered from the stem cell studies could potentially lead to treatments, or even cures, for diseases caused by chronic inflammation like atherosclerosis, arthritis, and even some cancers that progress due to inflammation.

Sarah Anderson, a student studying Economics at the University of North Carolina, Chapel Hill, was diagnosed with juvenile rheumatoid arthritis (JRA) at age three. JRA affects more than 250,000 children. Since then, she has lived with the burden that inflammatory disease has on a patient and loved ones.

“I’ve been through it all—oral medications, steroid injections, which are super painful because they have to get directly to the bone, physical therapy, and now I’m on a weekly injection,” she said. “When initially being tested, and doctors telling my mom that it could be leukemia, she said that it was the worst year of her life.”

Although the steps toward treating larger scale diseases with this type of stem cell therapy will take time and additional progress in the lab, Levy and colleagues are optimistic about the future.

“We’re harvesting the knowledge that we already have to hopefully modify cells to go to any relevant organ that needs treating,” Levy said. “We see a lot of progress for autoimmune diseases and other inflammatory diseases.”

While researchers remain optimistic, patients, like Anderson, remain somewhat skeptical. “Since joint damage is a side effect of arthritis, when not treated, I would want to see how this medication works long term,” she said. “I would love a cure one day or to stop these inconvenient injections, but when it comes to my health, I need to know with certainty that the benefits outweigh any costs.”

Now, Anderson is on a weekly regime of injections and says that after suffering for 17 years she has finally controlled her symptoms. “I have only been off medication for one year over the last 17 and that was when I was in remission in second grade,” she said. “Luckily today, even though I am not in remission, I do have it under control, but the future remains a mystery.”

Researchers say that though they are making progress with the development of the drug, there will not be an opportunity for public use for several years.

“We’ll keep on trying and keep on optimizing the process until we get a maximal response,” Levy said. “We’ll keep an open mind until we solve it.”

New Laser-based Tool for Brain Tumor Detection

By Kate Wheeling
BU News Service

Brain tumor surgery is a balancing act. Cut out too much and your patient leaves with neurologic damage; too little and the tumor grows back. Surgeons use MRIs to locate tumors, but in the operating room they’re left with visual and tactile cues – discoloration here, a firm spot there – to guide them around tumors. These methods are surprisingly imprecise for a field in which precision is critical.

Stimulated Raman scattering microscopy brain tumor image
Image courtesy of Minbiao Ji/Harvard University
Image of human glioblastoma tumor (blue) in mouse brain made by stimulated Raman scattering microscopy.

Now researchers at Harvard University and the University of Michigan are applying Stimulated Raman Scattering Microscopy, a technique recently developed in Dr. Sunney Xie’s Harvard laboratory, to differentiate between tumors and healthy tissue on a microscopic scale.

A study to evaluate the technique, published in September in Science Translational Medicine, focused on a tumor type called glioblastomas that grow winding tendrils throughout the brain. Glioblastomas are a particularly aggressive form of brain tumor – patients rarely survive more than a year after diagnosis. Tumor cores are easy to spot because they are crowded with dying cells, but the edges can be tricky. Tumor edges are a mixture of tumor cells and healthy tissue, making it impossible to tell where the tumor ends and normal tissue begins.

That is why these tumors recur “almost universally,” says Dr. Daniel Orringer, a neurosurgeon at the University of Michigan and co-author on the study. According to Orringer, surgeons routinely leave behind tumor cells that could have been safely removed. They just can’t see them under standard operating conditions.

To test whether Stimulated Raman Scattering Microscopy could help surgeons visualize tumor margins, researchers implanted human glioblastoma cancer cells into mice and waited for them to grow into tumors. Then they placed a laser scanning microscope over a hole in the skull of live mice and focused laser beams over a single focal spot of tissue at a time. The lasers caused different tissue types (e.g. healthy, lipid-rich brain tissue or protein-rich tumor tissue) to vibrate at different intensities. A computer program turned the vibrational signals from each point into a color-coded picture of the brain in real time, where tumor cells appeared blue and normal brain as green.

Using these computer generated images, researchers could distinguish tumors in tissue that appeared normal with standard techniques. Then when the group used the microscopy technique on human brain tissue samples, they found that the same cues used to distinguish tumor and normal tissue in mice held up in human tissue.

The group hopes to use Stimulated Raman Scattering Microscopy to maximize tumor removal and optimize surgical outcomes in humans, but right now the apparatus is too cumbersome for human applications. “What I would like to be able to do and what my colleagues tell me is possible to do is to develop a toothbrush-sized probe that we can place into someone’s head during surgery,” Orringer explained.

A prototype of this probe already exists, but several obstacles keep it from operating rooms. The concept needs to be validated using more human tissue samples and animal studies of the probe itself will need to be carried out. Aside from probe development, the group needs to build new lasers to achieve the same image quality in surgery that they had in the lab. They’re teaming up with two start-ups, Invenio Imaging and AdvancedMEMS, to address these engineering problems.

The cost may end up impeding biomedical applications even more than the technological obstacles, but experts say it’s worth it. Jerome Mertz, Professor of Biomedical Engineering at Boston University explains, “It’s a very expensive technique, but it’s really the only way to do what they’re doing.”

Harvard/MIT Scientists Invent Light Sabers…Basically.

By Cassie Martin
BU News Service

Hold on to your seats, Star Wars fans, because what I’m about to tell you is seriously cool. Scientists from Harvard and MIT have created a new form of matter that they are comparing to light sabers.

One of the lead researchers behind this discovery, Harvard Physicist Mikhail Lukin, said in a written statement “The physics of what’s happening in these molecules is similar to what we see in the movies.” Excuse me while my inner nerd jumps up and down with joy.

Toy versions of Luke Skywalker and Darth Vader battle in this recreated scene from Star Wars: Return of the Jedi. Photo courtesy of JD Hancock, Flickr Creative Commons.
Toy versions of Luke Skywalker and Darth Vader battle in this recreated scene from Star Wars: Return of the Jedi. Photo courtesy of JD Hancock, Flickr Creative Commons.

But what is happening, exactly?

Essentially, the researchers created an environment where mass-less photons (light particles) interact so strongly with one another that they act as though they have mass and bind together, forming molecules. But Lukin and his colleagues didn’t use the force to bind the photons together. No, they needed something more substantial.

The researchers pumped a rubidium (highly reactive metal) atom cloud into a vacuum, cooled it to just above absolute-zero, and fired two photons into the cloud using a weak laser. The photons emerged from the cloud stuck together thanks to what’s called the Rydberg blockade — an effect where one photon has to pass off its energy to an atom and move forward before a second photon can excite other nearby atoms. This results in the two photons pushing and pulling each other through the cloud, Lukin explained. “…when they exit the medium they’re much more likely to do so together than as single photons,” he said. The research was published in Nature online September, 25.

No word yet on the creation of real light sabers (one can only hope), but there are potential practical applications for this new discovery including quantum computing and the formation of 3-D structures completely out of light.

Food Physics: Dessert Edition

By Cassie Martin

It’s that time of year again, readers! Every week from September through December, hundreds of people line the halls of Harvard University eagerly waiting to get their hands on one of the hottest tickets in town and a chance to sample some truly delectable creations. If you love food and are even mildly interested in science, then Harvard’s free lecture series, Science + Cooking: From Haute Cuisine to the Science of Soft Matter, is the place to be.

Last night’s lecture featured Bill Yosses, the White House pastry chef and frequent contributor to the series. He kicked-off the night with a Youtube video of two Tesla coils playing House of the Rising Sun. At first I thought it was a techno cover until I saw the bolts of electricity flash across the screen. “Oh, this is gonna be good,” I thought.

Yosses presented the concept of elasticity and how it informs the texture and flavor of desserts to make for an incredible dining experience. The first half of the lecture felt like a high school physics class. We watched cool, old-timey gadgets build up and discharge static electricity; we watched Yosses bend the glowing green ray inside of a cathode ray tube with a magnetic field; we brushed up on surface tension; and we picked up some cool science history facts along the way. 

Did you know that Benjamin Franklin used one of the gadgets–called a Leyden jar–in his infamous kite experiment? Neither did I. Franklin’s portrait is also the only portrait in the White House not of a president or first lady.

White House Pasty Chef Bill Yosses teaches the crowd about electricity and magnetism. He uses these concepts to create intricate desserts. Photo courtesy of Cassie Martin.
White House Pasty Chef Bill Yosses teaches the crowd about electricity and magnetism. He uses these concepts to create intricate desserts. A Leyden jar can also be seen in the foreground. Photo courtesy of Cassie Martin.

After a quick overview of the science, the demonstrations began. Yosses’ demos covered some building blocks of desserts including foam, gel, and sugar–here are the coolest ones:

Peaches are one of my favorite fruits, so when he brought out peach puree to make foam I was excited, hoping I would get to taste it. Foam is a congregation of bubbles held together by surface tension and electrical charge that builds up between between the molecules. Immersion blenders are generally used to beat air into liquids, which releases more flavor molecules, according to Yosses. At one point, he pulled out a metal container brimming with fog. Liquid nitrogen is used by chefs to manipulate surface tension to get the right consistency (without adding unhealthy ingredients such as butter or oil) and preserve the flavor of food. It has a much lower boiling point than water, so it requires less energy to disrupt bonds which means that fewer flavor molecules are lost to heat. 

For one of the gel demos, which demonstrated bond formation and the cross-linking of molecules, he dipped a spoonful of hibiscus sauce into a mixture of water and a gelling agent (I’m unsure of it’s name). The gelling agent bound to the sauce, forming a skin around the outside. “It’s like an egg yolk, still liquid in the middle,” he said. After a few minutes, he scooped out a purple ball and added it to the plate of desserts.

Yosses ended the evening sculpting, but it looked more like glass-blowing. Under a red heat lamp sat a blob of sugar stuck between liquid and solid phases. Chefs commonly refer this as glass–the sugar is malleable, has a shiny quality, and becomes very brittle once it cools. Initial heating to 320 degrees Fahrenheit disrupts the crystalline structure resulting in a soft consistency, but the structure reforms upon cooling. Yosses carefully stretched the ball of sugar, wrapping small strands around a plastic stick. When he removed the wrapped strands of sugar from under the heat lamp, he was left with a hardened sugar coil which was promptly added to the dessert plate.

A plate of sugar and gelatin based desserts made by manipulating their molecular structure. Photo courtesy of Cassie Martin.
A plate of sugar and gelatin based desserts made by manipulating their molecular structure. Photo courtesy of Cassie Martin.

The Take Away:

Molecular gastronomy is giving chefs new tools and re-purposing old ones to make food better–not just by improving how a dessert looks or tastes, but it’s healthfulness too. Manipulating food at the molecular level makes it possible to achieve the same textures and flavors without adding notoriously unhealthy ingredients such as butter, oil, and fat. Yosses hopes his legacy will be known for “including desserts as part of a healthy diet, restoring food as a pleasurable experience, and preserving flavor,” he said.

The Critique:

The lecture was fun and informative. I learned something new and I sampled cocoa beans and fruit gel–can’t get much better than that. The one criticism I have is that there were a few times where I was unsure of how the science applied to his cooking techniques. I wish he would have explained the science alongside his demos instead of separating the two, so I could get a better understanding of what I was watching.