Published by
Stanford Medicine

Category

Bioengineering

Applied Biotechnology, Bioengineering, Immunology, Research, Stanford News, Stem Cells

Alchemy: From liposuction fluid to new liver cells

Alchemy: From liposuction fluid to new liver cells

alchemyHow’s this for modern-day medical alchemy: A team led by Stanford’s Gary Peltz, MD, PhD, has found a fast, cheap, efficient way for regenerating liver tissue from a patient’s own fat cells. Let it be immediately said that the “patients” in this endeavor (described in a just-published study in Cell Transplantation) were mice. But the fat cells that Peltz’s team used as starter materials and the liver tissue that grew inside the mice (replacing their own organs, which had experienced severe poisoning not unlike that caused by a Tylenol overdose) were completely human.

The liver – the body’s chemistry set – builds complex biomolecules we need and filters and breaks down waste products and toxic substances we need to get rid of. Unlike most organs, a healthy liver can regenerate itself to a significant extent. But this ability is no match for acute liver poisoning or damage from chronic alcoholism or viral hepatitis. Acute liver failure from acetaminophen (Tylenol) alone takes a toll of about 500 lives every year and accounts for upwards of 60,000 emergency-room visits annually.

That begets an ongoing, life-threatening liver shortage. From my release on the study:

Some 6,300 liver transplants are performed annually in the United States, with another 16,000 patients on the waiting list. Every year, more than 1,400 people die before a suitable liver can be found for them. While it can save lives, liver transplantation is complicated, risky and, even when successful, fraught with aftereffects. Typically, the recipient is consigned to a lifetime of taking immunosuppressant drugs to prevent organ rejection.

Making new livers out of a patient’s own readily retrieved fat tissue could help plug the gap between the number of available donor livers for transplantation and the number of people in dire need of that procedure. It might also go a long way to alleviating the requirement for lifelong immunosuppressant therapy afterward.

Peltz’s team obtained adipose stem cells, which ordinarily grow up to be fat cells, from fat-filled fluid removed during routine liposuction procedures. The team then put these cells through a series of biochemical hoops that caused them to change their minds and decide to be liver cells instead.

That’s not easy. (“We had to work hard to convert them to liver cells,” Peltz told me.) But it’s been done before. The problem was that previous fat-to-liver methods took longer than a patient with acute liver failure can survive, and were inefficient and expensive to boot. Using a new technique, Peltz’s group was able to get enough good liver cells for the next regenerative step – injecting the cells into mice’s liver cavities – within seven or eight days. A month later the mice exhibited healthy human liver formation and activity. Importantly, inspection at two months out showed no signs of tumor formation, which is a big obstacle to the alternative use of human embryonic stem cells or induced pluripotent stem cells for this purpose.

Peltz hopes to see the new technology enter clinical trials within a couple of years.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Free database of drugs associated with liver injury available from NIH and Hepatitis C virus’s Achilles heel
Photo by Abode of Chaos

Bioengineering, Events, Research, Stanford News

Nobel Laureate Michael Levitt at press conference: “Science is a passion”

Nobel Laureate Michael Levitt at press conference: “Science is a passion”
Stanford President John Hennessy; Michael Levitt, PhD; Dean Lloyd Minor, MD,  Stanford School of Medicine; and Jennifer Widom, PhD, department chair, computer science.

Stanford President John Hennessy, PhD; Michael Levitt, PhD; Lloyd Minor, MD, dean of the School of Medicine; and Jennifer Widom, PhD, chair of computer science

“There actually are websites where people make predictions about who will get the Nobel Prize, and I’m happy to report I wasn’t on any of them,” said Stanford’s new Nobel Laureate Michael Levitt, PhD, who charmed the audience with his wit and humility, at a press conference held on campus earlier today.

Levitt explained how he started his groundbreaking work when he was a 20-year-old postdoctoral scholar in Cambridge, England. Working mostly from home with his newborn child amidst stacks of computer punch cards, he began building the foundational software algorithms that now allow researchers to simulate complex biological processes within the body.

“He was a computer hacker when that was a good thing to be,” said Stanford President John Hennessy, PhD.

At 66, it’s obvious that Levitt is still thrilled to go into work every day. “This week we actually made progress on three difficult problems,” he said. “It’s remarkable when you get to do what you like. You end up working with smart young people… who get younger every year.”

When asked about his heroes, he quoted the French-American sculptor Louise Bourgeois, who at 70 indignantly told someone at her Museum of Modern Art exhibit, “You think this is a retrospective? I’m just beginning.” Afterwards she used the exhibit proceeds to rent a Brooklyn warehouse and went on to create her most famous work, including a series of enormous bronze spiders.

“That’s kind of how I want to be,” said Levitt about his post-Nobel plans. “Science is a passion.”

The full press conference can be watched here.

Previously: No average morning for Nobel winner Michael Levitt, Nobel winner Michael Levitt’s work animates biological processes and Stanford’s Michael Levitt wins 2013 Nobel Prize in Chemistry
Photo by L.A. Cicero/Stanford News Service

Bioengineering, Genetics, Stanford News, Videos

Nobel winner Michael Levitt’s work animates biological processes

Nobel winner Michael Levitt’s work animates biological processes

Proteins control nearly all of life’s functions, but how they self-assemble or fold is an unsolved problem in biology. Understanding how folding goes awry could lead to cures for diseases such as Alzheimer’s and Parkinson’s, which are caused by protein misfolding.

One of the winners of the 2013 Nobel Prize in Chemistry, Michael Levitt, PhD, is an early pioneer in “computational biology,” the development of complex software algorithms that allow researchers to simulate and experiment with biological processes such as protein folding. In 1969, he realistically modeled tRNA, a helper molecule for building proteins inside the body. He also discovered the architectural patterns in proteins, devised a protocol for simulating how water interacts with proteins and designed the first simulations of humanized antibodies.

In this video, Levitt’s Stanford colleague, Vijay Pande, PhD, shows a simulation of protein folding, and explains why computational biology is important to the future of medicine. By modeling protein folding, Pande says, “We hope to get exquisite detail and information that you might not be able to get from experiments.”

Previously: Stanford’s Michael Levitt wins 2013 Nobel Prize in Chemistry

Bioengineering, Medical Schools, Stanford News

Stanford’s Clark Center, home to Bio-X, turns 10

2532648329_1c08aaaf3bNot every academic research center is known for its social vibe or aesthetic appeal, but Stanford’s James H. Clark Center gets scientists to look up from their microscopes and appreciate the view.

The three-story, 146,000-square-foot research center houses Stanford Bio-X, which comprises biology, medicine, chemistry, physics and engineering and takes an interdisciplinary approach to creating new knowledge of biological systems for the benefit of human health.

As Stanford Report notes, the Clark Center, which is celebrating its 10th anniversary, was “created as a social experiment in collaboration.” Facets of the architecture, such as an open courtyard at the center of the complex, facilitate social gatherings. The round space has also welcomed events, concerts, and a site-specific dance piece (watch at 2:20-4:15 here).

Bio-X director Carla Shatz, PhD, told Robin Wander, “Not only are the space and the aesthetics gorgeous, but the labs are state of the art and the ability to flow from one lab to the next is liberating after spending years in research buildings with long hallways.”

From Stanford Report:

“The architecture of the Clark Center provided the catalyst for developing a master plan and an architectural ‘kit of parts’ that has established a strong and consistent identity for the School of Medicine precinct,” said David Lenox, director of campus planning. “The floating red roof lid, the limestone cladding and the proportion of the fenestration of the Clark Center inspired the design of the Li Ka Shing Center for Learning & Knowledge as well as the Lorry I. Lokey Stem Cell Research Building.”

Shatz reflects on Bio-X and the Clark Center’s history in a new 1:2:1 podcast with the medical school’s chief of communications, Paul Costello.

Photo by Stanford Live

Applied Biotechnology, Bioengineering, In the News, Stanford News, Technology

Project demonstration today: Stanford’s bioengineering boot camp for high schoolers

Project demonstration today: Stanford's bioengineering boot camp for high schoolers

Flanked by 18-year-old Zoe Nuyens (left) and 17-year-old Justine Sun, Alex Lee, also 17, demonstrates a system for detecting surgical gauze that was designed by local high school students. The trio were among the 26 students who attended at a bioengineering "boot camp" held at Stanford University.This summer, a group of 26 high-school students participated in Stanford’s first bioengineering boot camp. Based on the story in yesterday’s Stanford Report, I think it’s safe to say these students have a pretty enviable response to the age-old question, “What did you do in school today?”

For starters, they invented a way to help surgeons track and retrieve the gauze placed inside of patients during medical procedures.

Tom Abate describes the origins of “smart gauze” and the new boot camp here:

“Surgical sponges are the most common item left behind in surgeries and they’re very difficult to detect,” said [17-year-old Alex] Lee, who was one of 26 participants in a free, six-week bioengineering boot camp for high school students organized by Stanford undergraduate Stephanie Young.

Young, a bioengineering student who grew up in San Mateo, Calif., said she got the idea for the boot camp last year after talking with a friend who had gone through a similar intensive summer program in the law.

The boot camp employed the learning-by-building approach honed by Stanford’s Product Realization Lab, a teaching environment that offers design and prototyping facilities in support of student product creation. The high school students were presented with a series of real-world challenges and grouped into teams to devise solutions, which they then fashioned in the lab.

The camp’s high school students will demonstrate their designs today from 2 to 5 p.m. at the medical school’s Li Ka Shing Center for Learning and Knowledge. This special presentation is open to the public.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.

Previously: Image of the Week: CIRM intern Christina Bui’s summer project and Image of the Week: CIRM intern Brian Woo’s summer project
Photo, of students demonstrating a system for detecting surgical gauze, by Steve Castillo

Bioengineering, In the News, Neuroscience, Research, Stanford News

Short and sweet: Three days in a sugar solution, and you’ve got your see-through tissue sample

Short and sweet: Three days in a sugar solution, and you've got your see-through tissue sample

In a Nature Neuroscience report posted online yesterday, Japanese researchers at the RIKEN Center for Developmental Biology show how they’ve grabbed a ball tossed by Stanford psychiatrist/ neuroscientist/bioengineer Karl Deisseroth, MD, PhD, and run with it.

In April, Deisseroth’s team announced an amazing new method for transforming biological tissues (in this case, the brain of a rat) into, essentially, a transparent 3-D replica of itself replete with all its cells and even the proteins that sit on their surfaces. The breakthrough was achieved by using a chemical mixture to dissolve away the fatty materials that, while critical to the function of cells and tissues, is also largely responsible for their lack of transparency.

Getting transparent tissue samples via that method, dubbed CLARITY, required a couple of weeks and some pretty nasty chemicals. But it worked. And by doing so, it meant that scientists would for the first time be able to study, in exquisite detail, an intact tissue sample or even an entire organ without having to first slice it into dozens or hundreds of razor-thin sections, with all the distortion such mechanical manipulation wreaks and without the benefit of being able to view, say, intact nerve tracts. It was a big deal.

But innovation is contagious (and no true scientist would have it any other way). And now, with the latest discovery, no more noxious chemicals! You just toss a tissue sample into a jar of fruit juice (okay, technically “an aqueous fructose solution”) for a few days, and out comes your see-through sample.

Nope. That’s not an ice cube in there.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Peering deeply – and quite literally – into the intact brain: A video fly-through, Brain’s gain: Stanford neuroscientist discusses two major new initiatives and Image of the Week: 3-D rendering of a clarified brain
Photo by Breville USA

Bioengineering, Events, Genetics, Science, Stanford News

White House to highlight Stanford professors as “Champions of Change”

White House to highlight Stanford professors as "Champions of Change"

The White House will be honoring (.pdf) thirteen “Champions of Change” who are promoting and using open scientific data and publications to accelerate progress and improve our world.

Two Stanford professors — medical-systems expert Atul Butte, MD, PhD, and bioengineer Drew Endy, PhD — are among the entrepreneurs, academics, and researchers chosen for making an impact across disciplines and for helping make “open” the default in scientific research.

The White House Champions of Change program was created as part of President Obama’s Winning the Future initiative. Through this program, the White House highlights individuals, businesses, and organizations whose extraordinary stories and accomplishments positively impact our communities.

Live streaming of the event, which begins at 10 AM Pacific time tomorrow, will be available at  www.whitehouse.gov/live.

Previously: Atul Butte discusses why big data is a big deal in biomedicine, Obama’s new open-data policy aims to boost access to federal data for entrepreneurs, researchers, Strength in numbers: Harnessing public gene data to answer a diverse range of research questions and Better Know a Bioengineer: Drew Endy

Bioengineering, Imaging, Neuroscience, Research, Stanford News

Scientific community (and Twitter) buzzing over Stanford’s see-through brain

Scientific community (and Twitter) buzzing over Stanford's see-through brain

Yesterday’s announcement about Stanford scientists developing a process that renders tissue, specifically a mouse brain, transparent spurred a significant amount of excitement among both the scientific community and general public. We’ve captured the reactions in tweets, blog posts, videos and quotes from new articles on our Storify page.

Among the video content is an interview with Karl Deisseroth, MD, PhD, explaining the work, a fly-through of a complete mouse brain using fluorescent imaging, and commentary from Michelle Freund, PhD, a project officer in the National Institute of Mental Health Division of Neuroscience and Basic Behavioral Science, discussing the significance of the work. Mixed in with the videos are remarks from experts about how the breakthrough will advance the field of neuroscience and other research applications and candid comments from Twitter users. We hope the collection provides a broader perspective on the research and its potential to revolutionize cell biology.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact and Peering deeply – and quite literally – into the intact brain: A video fly-through

Bioengineering, Neuroscience, Research, Stanford News, Technology, Videos

Peering deeply – and quite literally – into the intact brain: A video fly-through

Peering deeply - and quite literally - into the intact brain: A video fly-through

Earlier today I wrote about a breakthrough method called CLARITY, pioneered by Stanford psychiatrist/bioengineer Karl Deisseroth, MD, PhD, for rendering intact tissue samples transparent. Above is a video clip showing off the new method’s capabilities. First you’ll witness a “fly-through” of a complete mouse brain using fluorescent imaging. The immediately following clip – it’s spectacular! – provides a three-dimensional view of a mouse hippocampus (the brain’s brain’s memory hub), with projecting neurons depicted in green, connecting interneurons in red, and layers of support cells, or glia, in blue.

Note that in both cases, there was no need to slice the tissue into ultra-thin sections, analyze them chemically and/or optically and then laboriously “sew” them back together via computer algorithms in order to reconstruct a 3-D virtual image of the biological sample. All that was required, after performing the necessary hocus-pocus, was to ”send in the stain” (i.e., use histochemical means to paint different cell types different colors) and move the sample or camera lens or shift the latter’s focal length. Nice trick. With big implications for biomedical research.

Previously: Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Visualizing the brain as a Universe of synapses and A federal push to further brain research

Bioengineering, Neuroscience, Research, Science, Stanford News, Technology

Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact

Lightning strikes twice: Optogenetics pioneer Karl Deisseroth's newest technique renders tissues transparent, yet structurally intact

Stanford psychiatrist and bioengineer Karl Deisseroth, MD, PhD, spent much of this century’s first decade developing a revolutionary method for studying the brain: optogenetics. In 2010, Nature Methods  heralded optogenetics as its “method of the year.”

It looks as though lightning has struck the Deisseroth lab again.

Suppose, just for a moment, that you’re conducting espionage on a heavily guarded multi-story building strongly suspected to be an advanced nuclear-weapons facility. The building quickly proves utterly inaccesible. Fortunately, you manage (through methods too covert to be revealed here) to procure a floor plan. Nice going. Now, you know a lot about the floors themselves and a bit of cross-sectional detail on the bases of whatever’s sitting on them. Better than nothing.

Now, imagine - in fantasyland, anything goes – that you can don goggles enabling you to peer right through the building’s outer walls and directly observe its three-dimensional structure, including its concealed laboratories and the instruments and manufacturing machinery inside of them. Payday!

An analogous technique developed by Deisseroth promises to revolutionize cell biology. Exploring connections among, and contents within, the billions of cells in a chunk of tissue often involves slicing the chunk into ultra-thin sections, exposing each slice’s top and bottom surfaces for microscopy or histochemical and electrical manipulation. Sophisticated computation can stitch the slices back together (virtually), roughly reconstructing the sample’s three-dimensional structure. (That’s the floor plan I mentioned earlier.)

Unfortunately, all this sawing disrupts key connections within the tissue and distorts its constitutent cells’ geography. Plus, while those sections are thin, they’re not infinitely thin. Light and chemicals can penetrate only so far. Volumes of valuable information about their innards remains concealed.

Deisseroth’s paradigm-shifting method, called CLARITY, renders tissue transparent while leaving it structurally intact, yet accessible to large “detective” molecules scientist use to gain information about cells’ surface features and genetic contents. In a study just published in Nature, a group led by Deisseroth (who discusses his work in the video above) converted an entire adult mouse brain into an optically transparent, histochemically permeable replica of itself. The position and structure of proteins embedded in the membranes of cells and their intracellular organelles remained intact.

Okay, step back with me for a minute. Essentially, all cells are liquid-filled bubbles of oil. (Nerve cells are better visualized as long, branching, liquid-filled tubes whose walls are made of fat.) These oil/fat (in science-speak, “lipid“) bubbles and walls (“membranes”) both house and compartmentalize their contents, so operations inside them can be carried out in relative isolation. Dotting membranes’ surfaces are all kinds of proteins performing innumerable activities key to the health of the cells they enclose and the tissues those cells compose.

Evolution designed lipid membranes to be mostly impermeable to large molecules, and they happen to be opaque (or else we’d all be transparent). In a feat of chemical engineering, Deisseroth’s team replaced the lipids with, for all purposes, clear plastic. With their work, you could literally read a newspaper through the mouse’s brain. Formerly membrane-bound proteins remained anchored in the membranes’ doppelgangers, retaining their structures (a big deal, as a protein’s structure determines its function). The tissue was also nanoporous: It permitted bulky “reporter”molecules such as stain-carrying antibodies and strips of DNA to flow deep into the transformed tissue sample and out again.

Obviously you wouldn’t want to try this on yourself, although Plastic Man certainly seems to have worked out the kinks.

Previously: Researchers induce social deficits associated with autism, schizophrenia in mice, Anti-anxiety circuit found in unlikely brain region and Nature Methods names optogenetics its “Method of the Year

Stanford Medicine Resources: