Stem Cell Stories that Caught our Eye: Stem Cell Summit Roundup, Spinal Cords in a Dish and Stem Cell Tourism in the NFL

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Success at the World Stem Cell Summit. This week some of the biggest names in regenerative medicine descended upon San Antonio, Texas for the annual summit. Along with researchers from the world’s top universities, institutions and companies were members of CIRM, including CIRM President and CEO C. Randall Mills.

We’ve been publishing top highlights from the Summit all week here on the Stem Cellar. There’s also been detailed coverage in the local San Antonio press, including the local ABC station. And if you’d like to find out more about this year’s conference, be sure to visit @WSCSummit and #WSC14 on Twitter.

Scientists have found a way to grow spinal cords from embryonic stem cells in a petri dish. [Credit: Abigail Tucker/ MRC Centre for Developmental Neurobiology/ Wellcome Images.]

Scientists have found a way to grow spinal cords from embryonic stem cells in a petri dish. [Credit: Abigail Tucker/ MRC Centre for Developmental Neurobiology/ Wellcome Images.]

Growing Spinal Cords in the Lab. Tissue engineering, the process of using stem cells to build new tissues and organs, has been the Holy Grail for regenerative medicine. And while there has been some progress with engineering some organs, others—especially the spinal cord—have proven far more difficult. This is because the biodegradable scaffolding cannot be made correctly to grow complex and intricately connected nerve cells.

But now, a research team in Germany has grown complete spinal cords in the lab, pointing to a new strategy for treating those with irreparable spinal cord injuries.

As reported in The Guardian this week, Andrea Meinhardt of the Dresden University of Technology and her colleagues worked around the problem of scaffolding by employing a new method called self-directed morphogenesis, first developed by the late Yoshiki Sasai. According to The Guardian‘s Mo Costandi:

“Self-directed morphogenesis is a method for growing embryonic stem cells in a three-dimensional suspension. Cells grown in this way can, when fed the right combination of signaling molecules, go through the motions of development and organize themselves to form complex tissues such as eyes, glands and bits of brain.”

While preliminary, this research offers immense promise towards the ultimate goal: reversing the devastating effects of spinal cord injuries.

Stem Cells and the NFL. Despite the best efforts of experts, stem cell tourism continues to proliferate. A new study published this week in 2014 World Stem Cell Report (a special supplement to Stem Cells and Development) describes the latest example of people seeking unproven stem cell treatments: this time in the NFL.

New research from Rice University is suggesting that some NFL players are seeking out unproven stem cell treatments—oftentimes traveling abroad without fully understanding the risks. This poses serious problems not only for players but also for the NFL as a whole. As Co-lead author Kirsten Matthews elaborated in a news release:

“With the rise of new and unproven stem cell treatments, the NFL faces a daunting task of trying to better understand and regulate the use of these therapies in order to protect the health of its players.”

Specifically, 12 NFL players are known to have received unproven treatments at some point during the last five years, including star quarterback Peyton Manning who we’ve blogged about before The authors caution that high-profile players broadcasting that they are receiving these unproven therapies could influence regular patients who are also desperate for cures.

In order to fix this growing problem, the authors recommend the NFL review and investigate these unproven stem cell treatments with the help of an independent committee of medical professionals. Finally, they suggest that the NFL could support stem cell research here in the United States—so that proven, effective stem cell-based treatments could more quickly enter the clinic.

At World Stem Cell Summit improvements in the precision with which we can edit our genes grabs spotlight

Just a day and a half into this year’s World Stem Cell Summit in San Antonio and there have been numerous highlights. But a pair of sessions on gene editing grabbed the attention of many of the scientists at the meeting. One of the renown leaders in the field, Harvard’s George Church wowed the scientists, but I fear the heavy dose of scientific detail may have overwhelmed many of the patient advocates that make the attendee mix at this meeting special.

George Church speaking recently [Credit: PopTech.org]

George Church speaking recently [Credit: PopTech.org]

In 2013, Church first published results using a new gene-editing tool he helped perfect called CRISPR, and almost immediately it became the most talked-about tool for advancing stem cell research. As powerful as stem cells may be by themselves, in many situations, they become even more powerful—especially if you use them to deliver a gene that corrects an error in a patient’s cells. Before 2013 we had a few ways to edit genes in living cells and all were modestly effective at making the desired change and relatively specific in making only a few unwanted changes, called “off target” edits.

In some uses, particularly when cells are being modified in the lab for specific and small targets, these other editing techniques are probably OK. This is what several CIRM-funded teams (links) are doing with diseases like sickle cell anemia and HIV, where you can target blood-forming stem cells and even giving a small percentage the proper gene edit may be sufficient to cure the disease. But with something like muscular dystrophy where the gene editing would be required throughout the body and have to be done in the patient not in the lab, you need to improve the efficiency and precision.

CRISPR/Cas9 [Credit: University of California, San Francisco]

CRISPR/Cas9 [Credit: University of California, San Francisco]

After that first publication CRISPR was viewed as a home run in efficiency, taking the number of cells with the gene correction from a few percent to 50 percent or more. But it still had off-target effects. Yet only a year after the technology was introduced, a few teams developed so-called “next generation” CRISPR that comes close to perfect precision, causing an unintended edit in just one in a billion cells, by Church’s estimate.

I have never seen the full name of CRISPR spelled out in a scientific presentation, and after a visit to Wikipedia I know why. Here it is: Clustered Regularly Interspersed Short Palindromic Repeats. Basically, Church took advantage of something that occurs naturally in many bacteria. Just as we are susceptible to viruses, bacteria have their version known as phages. When those parasites integrate their DNA into the bacteria’s genes, part of the bacterial DNA forms CRISPRs that can partner with a protein called Cas to cut the phage DNA and keep the phage from hurting the host bacteria.

In a research setting, creating that “nick” in the DNA is the first step in harnessing CRISPR to insert a desired gene. So, that extreme precision in finding spots on our DNA where we want to create an opening for inserting a new gene became this valuable research tool. It can create a nick as precise as a single nucleotide base, the building blocks of our DNA.

Church and two additional speakers gave detailed descriptions about how the technology has improved and how it is being used to model disease today and is expected to be used to treat disease in the near future. An exciting future is in store.

Don Gibbons

Truth or Consequences: how to spot a liar and what to do once you catch them

Nothing undermines the credibility of science and scientists more than the retraction a high profile paper. Earlier this year there was a prime example of that when researchers at one of Japan’s most prestigious research institutions, the Riken Center for Developmental Biology in Kobe, had to retract a study that had gathered worldwide attention. The study, about a new method for creating embryonic-like stem cells called stimulus triggered acquisition of pluripotency or STAP, was discredited after it was discovered that the lead author had falsified data.

Publication retractions have increased dramatically in recent years [Credit: PMRetract]

Publication retractions have increased dramatically in recent years [Credit: PMRetract]

The STAP incident drew international coverage and condemnation and raised the question, how common is this and what can be done to combat it? A panel discussion at the World Stem Cell Summit in San Antonio, Texas entitled “Reproducibility and rigor in research: What have we learned from the STAP debacle” tackled the subject head on.

Ivan Oransky, medical journalist and the co-founder of the website Retraction Watch posed the question “Does stem cell research have a retraction problem?” He says:

“The answer to my question is yes. But so does everyone else. All of science has a retraction problem, not just stem cells.”

Oransky says the number of retractions has doubled from 2001 to 2010. One author has retracted 183 times – the record so far – but to break into the top 5 you need to have at least 50 retractions. These come from all over the world from the US to Germany and Japan and most recently Azerbaijan.

Oransky says part of the problem is the system itself. Getting your research results published is critical to advancing a career in science and those kinds of pressures force people to cut corners, take risks or even just falsify data and manipulate images in order to get a paper into a high profile journal. In most cases, journals charge a fee of several hundred to thousands of dollars to publish studies, so they have no incentive to dig too deeply into findings looking for flaws, as it might undermine their own business model.

“Some authors, more than 100, have been caught reviewing their own papers. When the journal they were submitting their paper to asked for the names of recommended reviewers they would submit the names of people who are legitimate reviewers in the field but instead of giving real email addresses they would give fake email addresses, ones they controlled so they could submit their own reviews under someone else’s name.”

What gave them away is that all the potential “reviewers” didn’t first reply and say “yes, I’ll review”, instead they responded by sending back a full review of the paper, raising suspicions and ultimately to detection.

Graham Parker, a researcher at Wayne State University School of Medicine and the editor of Stem Cell and Development says spotting the problem is not always easy:

“As an editor I regard scientific misconduct as fabrication, falsification or plagiarism of data but there are lots of other areas where it’s not always so clear – there are often shades of gray”

He says researchers may make an honest mistake, or include duplicative images and in those cases should be allowed to fix the problems without any stigma attached. But when serious cases of falsification of data are uncovered they can have a big impact by retarding scientific progress and sapping public confidence in the field as a whole.

Jeanne Loring, a stem cell scientist at The Scripps Research Institute and a recipient of funding from CIRM, says the STAP incident was actually a sign of progress in this area. Ten years ago when a Korean researcher named Hwang Woo-Suk claimed to have cloned human embryos it took more than a year before he was found to have falsified the data. But in the STAP case it took a little over a week for other researchers to start raising red flags:

“One of the real heroes in this story is Paul Knoepfler (a CIRM-funded researcher at UC Davis) who takes on difficult issues in his blog. It took Paul just 8 days to post a request for people to crowdsource this study, asking people who were trying to replicate the findings to report their results – and they did, showing they failed over and over again”

Parker said it’s getting easier for editors and others in the field to double check data in studies. For example new software programs allow him to quickly check submitted manuscripts for plagiarism. And he says there is a growing number of people who enjoy looking for problems.

“Nowadays it’s so easy for people to dig very deeply into papers and check up on every aspect of it, from the content to the methodology to the images they use and whether those images were in any way manipulated to create a false impression. Once they find a problem with one paper they’ll dig back through papers in that scientist’s past to see if they can find other problems dating back years that were never found at the time.”

He says that in most cases researchers caught falsifying data or deliberately misleading journals faced few consequences:

“Often the consequences of misconduct are very mild, the equivalent of a slap on the wrist, which does not discourage others from trying to do the same.”

Each panel member says that tougher penalties are needed. For example, in extreme cases a threat of criminal action could be warranted, if the falsified research could lead to serious consequences for patients.

But the panel ended on an encouraging note. Oransky says, for example, that medical journals are now paying more attention and imposing stricter rules and he says there’s even scientific evidence that “doing the right thing might pay off.”

“One study recently showed that if you made an honest error and corrected it publicly not only does the stigma of retraction not apply to you, you don’t get a decrease in your citations—you actually get an increase. So we’d like to think that doing the right thing is a good thing and might actually be a positive thing.”

Taking Promising Therapies out of the Lab and into People: Tips from Experts at the World Stem Cell Summit on How to Succeed

Having a great idea for a stem cell therapy is the easy part. Getting it to work in the lab is tougher. But sometimes the toughest part of all is getting it out of the lab and into clinical trials in patients. That’s natural and sensible, after all we need to make sure that something seems safe before even trying it in people. But how do you overcome all the challenges you face along the way? That was the topic of one of the panel discussions at the World Stem Cell Summit in San Antonio, Texas.

Rick Blume is the Managing Director at Excel Venture Management, and someone with decades of experience in investing in healthcare companies. He says researchers face numerous hurdles in trying to move even the most promising therapies through the approval and regulatory process, only some of which are medical. Blume says:

“Great ideas can become great companies. And good Venture Capitalists (VCs) can help with that process, but the researchers have to overcome technical, funding and logistical hurdles before VCs are usually ready to move in and help.”

Of course that’s where agencies and organizations like CIRM come in. We help fund the early stage research, helping researchers overcome those hurdles and getting promising therapies to a point where VCs and other large investors are willing to step in.

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Left to right: Geoff Crouse CEO of Cord Blood Registry, C. Randal Mills, President and CEO of CIRM, Rick Blume of Excel Venture Management and Anthony Atala of Wake Forest University Medical Center

Geoff Crouse, the CEO of the Cord Blood Registry, says researchers need to be increasingly imaginative when looking for funding these days.

“While Federal funding for this kind of research is drying up, there are alternatives such as CIRM and philanthropic investors who are not just seeking to make active investments but are also trying to change the world, so they offer alternatives to more traditional sources of funding. You have to look broadly at your funding opportunities and see what you want to do.”

C. Randal Mills, the President and CEO of CIRM said too many people get caught up looking at the number of challenges that any project faces when it starts out:

“The single most important thing that you need to do is to show that the treatment works in people with unmet medical needs, that it is safe. If you can do that, all the other problems, the cost of the therapy, how to market it, how to get reimbursed for it, those will all be resolved in time. But first you have to make it work, then you can make it work better and more efficiently.”

The panel all agreed that one of the areas that needs attention is the approval and regulatory process saying the Food and Drug Administration (FDA) the regulatory body governing this field, needs to adjust its basic “one size fits all” paradigm.”

Mills says the FDA is in a difficult position:

“Everyone wants three things; they want fast drugs, they want cheap drugs and they want perfect drugs. The problem is you can’t have all three. You can have two but not all three and that puts the FDA into an almost impossible position because if therapies aren’t approved quickly they are criticized but if they are approved and later show problems then the FDA is criticized again.”

Often the easiest way to get a traditional drug therapy approved for use is to ask for a “humanitarian exemption”, particularly for an orphan disease that has a relatively small number of people suffering from it and no alternative therapies. But when it comes to more complex products knows as biologics, which includes stem cell therapies, this humanitarian exemption does not exist making approval much harder to obtain, slowing down the field.

Mills says other countries, such as Japan, have made adjustments to the way they regulate new therapies such as stem cells and he hopes the FDA will learn from that and make similar modifications to the way they see these therapies.

All three panelists were optimistic that the field is making good progress, and will continue to advance. Good news for the many patient advocates attending the World Stem Cell Summit who are waiting for treatments for themselves or loved ones.

Speak Friend and Enter: How Cells Let the Right Travelers through their Doors

For decades, it’s been a molecular mystery that scientists were seemingly unable to solve: how do large molecules pass through the cell and into the nucleus, while others half their size remain stranded outside?

These are nuclear pores imaged by atomic force microscopy, appearing as a craterlike landscape in which each crater corresponds to a pore of ~100 nm diameter. [Credit: UCL]

Nuclear pores imaged by atomic force microscopy, appearing as a crater-like landscape in which each crater corresponds to a pore of ~100 nm diameter. [Credit: UCL]

But as reported in the latest issue of Nature Nanotechnology, researchers now believe they may have cracked the case. By shedding light on this strange anomaly, University College London (UCL) scientists have opened the door for one day delivering gene therapies directly into the nucleus. With numerous research teams working on ways to merge stem cell therapy and gene therapy, this could be extremely valuable to our field.

Scientists already knew that the membrane that surrounds the cell’s nucleus is ‘punctured’ with millions of tiny holes, known as nuclear pores. Co-lead author Bart Hoogenboom likened the pores to a strange kind of sieve:

“The pores have been to known to act like a sieve that could hold back sugar while letting grains of rice fall through at the same time, but it was not clear how they were able to do that.”

In this study—which used cells taken from frog eggs—Hoogenboom, along with co-lead author Ariberto Fassati, harnessed atomic force microscopy (AFM) to give them a new understanding of how these pores work. Like a blind person moving their fingers to read braille, AFM uses a tiny needle to pass over the nuclear pores in order to measure their shape and structure.

“AFM can reveal far smaller structures than optical microscopes,” said Hoogenboom, “but it’s feeling more than seeing. The trick is to press hard enough to feel the shape and the hardness of the sample, but not so hard that you break it. [In this study], we used it to successfully probe the membrane…to reveal the structure of the pores.”

And what they found, adds Fassati, offered an explanation for how these pores worked:

“We found that the proteins in the center of the pores tangle together just tightly enough to form a barrier—like a clump of spaghetti. Large molecules can only pass through [the pores] when accompanied by chaperone molecules. These chaperones, called nuclear transport receptors, have the property of lubricating the [spaghetti] strands and relaxing the barrier, letting the larger molecules through.”

Astoundingly, Fassati said that this process happens upwards of several thousand times per second.

These results are exciting not only for solving a long-standing mystery, but also for pointing to new ways of delivering gene therapies.

As evidenced by recent clinical advances in conditions such as sickle cell disease and SCID (‘bubble baby’ disease), gene therapy represents a promising way to treat—and even cure—patients. Hoogenboom and Fassati are optimistic that their team’s discovery could lead further refinements to gene therapy techniques.

Said Fassati, “It may be possible to improve the design of current mechanisms for delivering gene therapy to better cross the nuclear pores and deliver their therapeutic genes into the nucleus.”

Spinal cord injury and stem cell research; find out the latest in a Google Hangout

Spinal cord injuries are devastating, leaving the person injured facing a life time of challenges, and placing a huge strain on their family and loved ones who help care for them.

The numbers affected are not small. More than a quarter of a million Americans are living with spinal cord injuries and there are more than 11,000 new cases each year.

It’s not just a devastating injury, it’s also an expensive one. According to the National Spinal Cord Injury Statistical Center it can cost more than $775,000 to care for a patient in the first year after injury, and the estimated lifetime costs due to spinal cord injury can be as high as $3 million.

Right now there is no cure, and treatment options are very limited. We have heard for several years now about stem cell research aimed at helping people with spinal cord injuries, but where is that research and how close are we to testing the most promising approaches in people?

That’s going to be the focus of a Google Hangout on Spinal Cord Injury and Stem Cell Research that we are hosting tomorrow, Tuesday, November 18 from noon till 1pm PST.

We’ll be looking at the latest stem cell-based treatments for spinal cord injury including work being done by Asterias Biotherapeutics, which was recently given approval by the Food and Drug Administration (FDA) to start a clinical trial for spinal cord injury. We are giving Asterias $14.3 million to carry out that trial and you can read more about that work here.

We’re fortunate in having three great guests for the Hangout: Jane Lebkowski, Ph.D., the President of research and development at Asterias; Roman Reed, a patient advocate and tireless champion of stem cell research and the founder of the Roman Reed Foundation; and Kevin Whittlesey, Ph.D., a CIRM science officer, who will discuss other CIRM-funded research that aims to better understand spinal cord injury and to bring stem cell-based therapies to clinic trials.

You can find out how to join the Hangout by clicking on the event page link: http://bit.ly/1sh1Dsm

The event is free and interactive, so you’ll be able to ask questions of our experts. You don’t need a Google+ account to watch the Hangout – just visit the event page at the specified time. If you do have a G+ account, please RSVP at the event page (link shown above). Also, with the G+ account you can ask questions in the comment box on this event page. Otherwise, you can tweet questions using #AskCIRMSCI or email us at info@cirm.ca.gov.

We look forward to seeing you there!

Entrepreneurship and Education

Guest author Neil Littman is CIRM’s Business Development Officer.

CIRM works closely with UCSF on a number of initiatives, from providing funding to academic investigators to jointly hosting events such as the recent CIRM Showcase with J-Labs held at the Mission Bay campus.

Beyond our joint initiatives, UCSF also provides many other valuable resources and educational opportunities to the life sciences community in the Bay Area. For instance, I was a mentor in UCSF’s “Idea to IPO” class which focused on helping students translate concepts into a commercializable product and viable business.

Another opportunity that may be of interest to all you budding entrepreneurs is UCSF’s Lean LaunchPad course, which kicks off in January (application deadline is Nov 19th). The course teaches…

“scientists and clinicians how to assess whether the idea or technology they have can serve as the basis of a business. The focus is on the marketplace where you must validate that your idea has value in order to move into the commercial world.”

See more at: Lean Launchpad for Life Sciences & Healthcare.

The course is being run out of the Entrepreneurship Center at UCSF, which is a division of the UCSF Office of Innovation, Technology & Alliances (ITA).

Ideas and Energy Reveal Surprises at Stem Cell Showcase

Janssen, the company within the pharmaceutical giant Johnson & Johnson responsible for much of its research and development, has a branch in the Bay Area called J Labs. It seeks to foster innovation in all sectors of biomedical research. One piece of that effort brings together innovators for monthly gatherings to exchange ideas and network. The events have an upbeat sense of energy so it was exciting when they invited CIRM to put together an all-day session dubbed: CIRM Showcase: Accelerating Stem Cell Treatments to Patients.

logo

The resulting showcase yesterday had that energy. But for someone who knows the CIRM portfolio of projects backward and forward, I thought, there were a few pleasant surprises. Perhaps the most exciting news came from Linda Marban, CEO of Capricor, the company CIRM is funding to complete a clinical trial in patients with weakened hearts after a heart attack. She disclosed that the company’s next target is the heart remodeling that is the cause of death in most boys with Duchenne muscular dystrophy. She said some early data would be released at the American Heart Association meeting in Chicago in two weeks.

Another bit of news—most exciting for science wonks—came from the biotech company Sangamo that CIRM funds to develop genetically modified blood stem cells as therapy for two diseases, HIV and beta thalassemia. The firm has developed a molecular scissors called a zinc finger nuclease that can splice the DNA that makes our genes. I knew the technique was pretty precise, but Curt Herberts from the company said they had perfected it to where it could get down to a single base pair—a single link in the chain that makes up our DNA. This greatly reduces the chances for any unintended effects of the genetic manipulation.

Two advances I learned about were in using iPS type stem cells as models for disease and for discovery of traditional drugs to treat those diseases. Ashkan Javaherian, from Steve Finkbeiner’s lab at the Gladstone Institutes, described some results with the robotic microscope they have developed that lets them screen hundreds of molecules on neurons grown from iPS cells reprogrammed from patients with specific diseases. Looking just at compounds already approved by the Food and Drug Administration (FDA), ones that could be put in the clinic quickly, they found four that reduced the degradation normally seen in neurons grown from patients with Huntington’s disease.

Similarly, Joseph Wu of Stanford described his work with cells from families with various genetic heart disorders. In addition to getting individualized information from the patient-specific cells, he said they could now take it one step further and sequence the entire DNA of the cells for just $500, yielding the chance to find out exactly what mutations were causing the disease. He said it was a big step towards truly personalized medicine and to developing therapies for various racial groups that respond differently to drugs.

The day began with our President and CEO C. Randall Mills detailing his plans for a nimbler, more responsive CIRM he has dubbed CIRM 2.0. This crowd seemed thrilled with his plan for an open call for applications so that they could come in with a request when they are ready instead of forcing them into a premature application for funding because the window might not open for another year or two.

One bit of trivia drove home how difficult the entire process of moving innovative therapies into the clinic can be. Paul Laikind, CEO of ViaCyte, the company CIRM has provided more than $50 million to develop a diabetes therapy, noted the size of the application they sent to the FDA: 8,500 pages. Kind of says it all.

Don Gibbons

Scientists Develop Stem Cell ‘Special Forces’ in order to Target, Destroy Brain Tumors

Curing someone of cancer is, in theory, a piece of cake: all you have to do is kill the cancer cells while leaving the healthy cells intact.

But in practice, this solution is far more difficult. In fact, it remains one of the great unsolved problems in modern oncology: how do you find, target and destroy each individual cancer cell in the body—while minimizing damage to the surrounding cells.

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

But luckily, Harvard Stem Cell Institute scientists at Massachusetts General Hospital may have finally struck gold: they have designed special, toxin-secreting stem cells that can target and destroy brain tumors. Their findings, which were performed in laboratory mice and which appear in the latest issue of the journal STEM CELLS, offer up an entirely unique method for eradicating deadly cancers.

Harvard Neuroscientist Khalid Shah, who led the study, explained in last Friday’s news release that the idea of engineering stem cells to kill cancer cells is not new—but there was a key difference in scientists’ ability to target individual cells vs. difficult-to-reach tumors, which is often the case with brain cancer:

“Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don’t work as well in solid tumors because the cancers aren’t as accessible and the toxins have a short half-life.”

The solution, Shah and his team argued, was stem cells. Previously, Shah and his team discovered that stem cells could be used to circumvent these problems. The fact that stem cells continuously renew meant that they could also be used to continually deliver toxins to brain tumors.

“But first, we needed to genetically engineer stem cells that could resist being killed themselves by the toxins,” said Shah.

In this study, the research team introduced a small genetic change, or mutation, into the stem cells so that they become impervious to the toxin’s harmful effects. They then introduced a second mutation that allowed the stem cells to maintain and produce and secrete toxins throughout the cells’ lifetime—effectively giving it an unlimited supply of ammunition to use once it encountered the brain tumor.

They then employed a common technique whereby the toxins were tagged so that they only sought out and infected cancer cells—leaving healthy cells unscathed.

“We tested these stem cells in a clinically relevant mouse model of brain cancer,” Shah described. “After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models.”

While preliminary, these results are encouraging. As the team continues to refine their method of development and delivery, they are optimistic that they can bring their methods to clinical trial within the next five years.

These Are the Cells You’re Looking for: Scientists Devise New Way to Extract Bone-Making Stem Cells from Fat

Buried within our fat tissue are stashes of stem cells—a hidden reservoir of cells that, if given the right cues, can transform into cells that make up bone, cartilage or fat. These cells therefore represent a much-needed store for regenerative therapies that rebuild bone or cartilage lost to disease or injury.

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). [Credit: Darling lab/Brown University]

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). The center image shows both types of cells prior to sorting [Credit: Darling lab/Brown University]

The only problem with these tucked-away cellular reservoirs, however, is identifying them and getting them out.

But now, researchers at Brown University have devised a unique method of identifying, extracting and then cultivating these bone-producing stem cells. Their results, published today in the journal Stem Cell Research & Therapy, seem to offer a much-needed alternative resource for growing bone.

Traditional methods attempting to locate and extract these stem cells focused on proteins that reside on the surface of the cells. Find the proteins, scientists reasoned, and you’ve found the cell.

Unfortunately, that method was not fool proof, and many argued that it wasn’t finding all the cells that reside in the fat tissue. So Brown scientists, led by Dr. Eric Darling found an alternative.

They knew that a gene called ALPL is an indicator of bone-making cells. If the gene is switched on, the cell has the potential to make bone. If it’s switched off, it does not. So Darling and his team devised a fluorescent marker, or tag, that stuck to the cells with activated ALPL. They then used a special machine to sort the cells: those that glowed went into one bucket, those that did not went into the other.

To prove that these ALPL-activated cells were indeed capable of becoming bone and cartilage, they then cultivated them for several weeks in a petri dish. Not only did they transform into the right cell types—they did so in greater numbers than cells extracted using traditional methods.

Hetal Marble, a graduate student in Darling’s lab and the paper’s first author, argues that tagging genes—rather than surface proteins—in order to distinguish and weed out cell types represents an important paradigm shift in the field. As he stated in a press release:

“Approaches like this allow us to isolate all the cells that are capable of doing what we want, whether they fit the archetype of what a stem cell is or is not. The paradigm shift is thinking about isolating populations that are able to achieve an end point rather than isolating populations that fit a strictly defined archetype.”

While their method is both precise and accurate, there is one drawback: it is slow.

Currently, it takes four days to tag, extract and cultivate the bone-making cells. In the future, the team hopes they can shorten this time frame so that they could perform the required steps within a single surgical session. As Darling stated:

“If you can take a patient into the OR, isolate a bunch of their cells, sort them and put them back in—that’s ideally where we’d like to go with this.”