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.”

Stem cell stories that caught our eye: heart disease, blindness and replacement teeth

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.

Review looks at approaches to blindness.
The Scientist published a nice lay level overview of various teams’ work to use stem cells to cure blindness. The bulk of the story covers age-related macular degeneration, the most common form of blindness in the elderly, with six approaches discussed and compared including the CIRM-funded California Project to Cure Blindness.

Dennis Clegg, one member of the California project team, was featured in a story posted by his university

The piece smartly includes an overview of the reasons eye diseases make up a disproportionate number of early stem cell trials using stem cells from sources other than bone marrow. Many in the field view it as the perfect target for early therapies where safety will be a main concern. It is a confined space so the cells are less likely to roam; it is small so fewer cells will be needed; and it has reduced immune activity so less likely to reject new cells.

The author describes three approaches to using cells derived from embryonic stem cells, one using iPS-type stem cells, one using fetal-derived nerve stem cells and one using cells from umbilical cord blood. An ophthalmologist from the University of Wisconsin who was not associated with any of the trials offered a fair assessment:

“We’re pushing the boundaries of this technology. And as such, we expect there to be probably more bumps in the road than smooth parts.”


A heart of gold, nanoparticles that is.
Most teams using scaffolds seeded with cells to create patches to strengthen damaged hearts start with animal material to create the scaffold, which can cause immune problems. An Israeli group has developed a way to use a patient’s own fat tissue to create these scaffolds. But that left the remaining problem of getting cells in a scaffold to beat in unison with the native heart. They found that by lacing the scaffold with gold nanoparticles they could create an effective conduction system for the heart’s electrical signals.

A story in ScienceDaily quotes the lead researcher Tal Dvir:

“The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds.”

If you read the story parts of it are a little overwrought. The headline, “A Heartbeat away? Hybrid patch could replace transplants,” pushes credibility on two fronts. The first half suggests this therapy is imminent, rather than the reality of years away. Patches could only replace the need for transplants. They could never work as well as a full new heart, but since we only need partial function in our heart to live relatively OK, and they might be safer than a transplant they might replace the need.

Could teeth be first complex organ stem cell success? The Seattle Times did a pretty thorough story about why the tooth might be the first complex organ replaced via stem cells and regenerative medicine. While it is a complex organ with multiple layers, a blood system and a nervous system, it does not have moveable parts and we understand each part better than with other major organs.

The paper starts with a good reminder of just how far dental hygiene has come, with few elderly people needing dentures today—leaving the need for new teeth, suggests the author, to people such as hockey players.

A CIRM-funded team is investigating various ways to build a new tooth.

Even the Tea Party would like this regulation.
We have roughly as many genes as a frog, but are much more complicated. Our higher function evolved in part by making our genes more highly regulated. A CIRM-funded team now reports that this particularly applies to our “jumping genes,” and no that does not have anything to do with jumping frogs.

The work focuses on transposons, bits of our DNA that literally move around, or jump, between our functional genes and change how they are turned on or off. We also have evolved a set of genes to control the jumping genes, and the researchers at the University of California, Santa Cruz, suggest that evolution has been a never ending tug of war between the jumping genes and the genes that are supposed to control them.

HealthCanal ran the university’s press release, which quotes lead researcher Sofie Salama:

“We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about.”

Don Gibbons

Seventh annual Stem Cell Awareness Day, Oct. 8, will share some of the reasons behind the hope

When we organized the first Stem Cell Awareness Day in 2008 it was a small affair with events in Australia, Canada and a couple venues in California. It has quickly grown to become a sufficiently grass roots event worldwide that we can’t capture all the activities. But we feature 10 events in the US and six international events at our web site stemcellday.com.

Last year's Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

Last year’s Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

One entry in particular is truly international: the opening of a science museum exhibit “Super Cells” in Canada before it embarks on a five-year tour across North America, the United Kingdom, and potentially Europe as well. We wrote about the exhibit that CIRM helped to develop last week.

One event that fully embraces the spirit of the day this year will be at the annual Stem Cell Meeting on the Mesa in La Jolla, California. All the various players in the field, researchers, industry executives and investors come together at this annual gather on the famous La Jolla mesa to foster partnerships that can accelerate the movement of discoveries into therapies for patients. These international leaders will be joined by the public at an event on the second night of the meeting. The featured speaker will be Carl June, a real star of one of the field’s breakthrough therapies: using genes to modify cells to treat cancer and HIV.

In California, CIRM-funded institutions in San Diego, Irvine, Los Angeles, Berkeley and Sacramento will be hosting lab tours, seminars and other events for the public. We will also be matching CIRM grantees with high schools up and down the state to offer guests talks on stem cell science. We expect to reach at least 50 classes and more than a thousand students. Similar efforts are taking place in Toronto, Canada and in New York State.

Many of the activities today and throughout the month—we consider all of October a time to share stem cell knowledge—are focused on the general public. A list of those we are aware of can be found on the Stem Cell Awareness Day website.
If you can’t make one of these events but want to discover more about stem cells, here are a few of our best resources:
stem cell basics
Disease fact sheets
A list of our therapies in development

This year attendees at all the events are likely to hear much more than in previous years about potential therapies that have made it through the pipeline and are now being tested (or close to being tested) in patients. The promise and hope of stem cell science is starting to be backed up by data.

Don Gibbons

See You Next Week: 2014 Stem Cell Meeting on the Mesa

Next week marks the fourth annual Stem Cell Meeting on the Mesa (SCMOM) Partnering Forum in La Jolla, California and CIRM , one of the main organizers, hopes to see you there.

SCMOM

SCMOM is the first and only meeting organized specifically for the regenerative medicine and cell therapy sectors. The meeting’s unique Partnering Forum brings together a network of companies—including large pharma, investors, research institutes, government agencies and philanthropies seeking opportunities to expand key relationships in the field. The meeting will feature presentations by 50 leading companies in the fields of cell therapy, gene therapy and tissue engineering.

Co-founded by CIRM and the Alliance for Regenerative Medicine (ARM), SCMOM has since grown both in participants and in quality. As Geoff MacKay, President and CEO of Organogenesis, Inc. and ARM’s Chairman, stated in a recent news release:

“This year the Partnering Forum has expanded to include an emphasis not only on cell therapies, but also gene and gene-modified cell therapy technologies. This, like the recent formation of ARM’s Gene Therapy Section, is a natural progression for the meeting as the advanced therapies sector expands.”

This year CIRM President and CEO Dr. C. Randal Mills, as well as Senior Vice President, Research & Development Dr. Ellen Feigal will be speaking to attendees. In addition, 12 CIRM grantees will be among the distinguished speakers, including Drs. Jill Helms, Don Kohn and Clive Svendsen, as well as leaders from Capricor, Asterias, ViaCyte, Sangamo Biosciences and others.

CIRM has made tremendous progress advancing stem cell therapies to patients and expects to have ten approved clinical trials by the end of 2014. The trials which span a variety of therapeutic areas using several therapeutic strategies such as cell therapy, monoclonal antibodies and small molecules are increasingly being partnered with major industry players. CIRM still has more than $1 billion to invest and is interested in co-funding with industry and investors—don’t miss the chance to strike the next partnership at SCMOM next week.

For more details and to view the agenda, please visit: http://stemcellmeetingonthemesa.com/

The sparrow’s dying song: a possible path toward natural, stem cell-based repair of human brain diseases

Songbird research? How the heck could studying tweeting birds lead to advancements in human health?

At a first glance, biological research in other organisms like bacteria, yeast, flies, mice and birds can seem frivolous and a waste of taxpayer money. Yet it’s astonishing how we humans share very similar if not identical functions at a cellular level with our fellow creatures on Earth. So unraveling underlying biological processes in less complex animals is essential to better understanding human biology and to finding possible paths for treating human disease.

Gambel's White-crown sparrow: could its song unlock methods for repairing the brain? (photo courtesy Lip Kee, wikimedia commons)

Gambel’s White-crown sparrow: could its song unlock methods for repairing the brain? (photo courtesy Lip Kee, wikimedia commons)

Case in point: research published in the Journal of Neuroscience last week suggests that studying brain stem cells in song birds could one day lead to methods for naturally repairing neurodegenerative disorders such as Alzheimer’s disease in humans.

The University of Washington team behind the report studies the seasonal song behavior of Gambel’s white-crown sparrows. During the spring breeding season, the population of cells in the sparrow’s brain that are responsible for singing double in number. This cell growth helps the bird to be at its peak singing performance for attracting mates and staking its territory. As breeding season recedes, these brain cells die away naturally and the sparrow’s song, no longer needed, deteriorates. When the next spring arrives the brain cells will grow again.

Audio tracing's of the sparrow's song show its degradation after breeding season each year. (T. Larson/Univ. of Washington)

Audio tracings of the sparrow’s song show its degradation after breeding season each year. (image: T. Larson/Univ. of Washington)

The team’s fascinating discovery is that the dying brain cells themselves appear to provide a signal that tells brain stem cells to multiply for the next breeding season. The scientific term for the cell die-off is called programmed cell death, or apoptosis (pronounced A-POP-TOE-SIS). There are chemicals available to block apoptosis signals. And when the research team administered these anti-apoptosis chemicals at the end of the breeding season, there was a significant reduction in newly dividing brain stem cells. This result shows that new brain stem cell growth depends on the death of brain cells associated with song.

The next step in the project is to identify the signal from the dying cells that stimulates new brain stem cell growth. Once identified, that signal could be harnessed to naturally stimulate new brain stem growth to help repair the loss of brain cells seen in aging, Parkinson’s or Alzheimer’s disease.

As he mentions in a university news story, Dr. Eliot Brenowitz, the senior author of the report, is optimistic about their prospects:

“There’s no reason to think what goes on in a bird brain doesn’t also go on in mammal brains, in human brains. As far as we know, the molecules are the same, the pathways are the same, the hormones are the same. That’s the ultimate purpose of all this, to identify these molecular mechanisms that will be of use in repairing human brains.”

To learn about CIRM-funded projects related to neurodegenerative disorders, visit our Alzheimer’s and Parkinson’s online fact sheets.

Stem cell stories that caught our eye: heart disease, premature infants and incontinence

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.

Decoding heart health and genetics in Asians. A study from CIRM grantee Joseph Wu at Stanford may point the way to using stem cells to solve problems caused by too many drugs being tested predominantly on white males. Ethnic variations to drug response too often get ignored in current clinical trials.

The Stanford team has used iPS type stem cells to create a disease-in-a-dish model of a genetic mutation that effects 500 million people, but mostly East Asians. The mutation disables the metabolic protein called ALDH2 and results in increased risk of heart disease and increases the risk of death after a heart attack. By growing heart muscle from stem cells made from the skin of patients with the mutation his team found that the defect alters the way the heart cells react to stress.

Wu suggests that drug companies one day may keep banks of iPS cells from various ethnic groups to see how their responses to drugs differ. Science Daily ran the university’s press release.

Stem cells may treat gut disease in premies.
A laundry list of medical challenges confronts premature babies, but few are as deadly as the intestinal disease that goes by the name NEC, or necrotizing enterocolitis. It strikes with no notice and can kill within hours.

140925100256-largeA team at the University of Ohio reports they have developed what may be a two-pronged attack on the disease. First, they found a biomarker that can predict which infants might develop NEC, and second they have tested stem cells for treating the intestinal damage done by the disease. In an animal model they found that a type of stem cell found in bone marrow, mesenchymal stem cells, can reduce the inflammation that causes the damage and that neural stem cells can repair the nerve connections disrupted by the inflammation.

While this explanation sounds straight forward, getting to that potential intervention was anything but a simple path. The university wrote an extensive feature detailing the many years and many steps the research team took to unravel this who-done-it that involves the gut’s extensive “brain” and immune system. Science Daily picked up the piece.

We recently posted a video about a project we fund using stem cells to develop a treatment for irritable bowel disease.

Fat stem cells tested in incontinence. For far too many older women laughing and coughing can lead to embarrassing bladder leaks. Several groups are working with various types of stem cells to try to strengthen the urinary sphincter and help patients lead a more normal life. A team at Cleveland Clinic now reports some positive results using the most easily accessed form of stem cells, those in fat.

They harvested patients’ own fat stems cells, grew them in the lab for three weeks and then mixed them with a collagen gel from cows to hold them in place before injecting them into the sphincter. Three of five patients passed “the cough test” after one year. Good results, but clearly more work needs to be done to yield more uniform results. Stem Cells Translational Medicine published the research and issued this press release.

Some researcher suspect starting with an earlier stage, more versatile stem cell might yield better results. One of our grantees is developing cells to treat incontinence starting with reprogrammed iPS type stem cells.

New course looks at where fact and fiction overlap. I am a big fan of almost any effort to blend science and the arts. A professor at the University of Southern California seems to agree. CIRM grantee Gage Crump will be teaching a course next spring about science fiction and stem cells.

The university says the course, Stem Cells: Fact and Fiction, will range from babies born with three biological parents to regrown body parts. The course will explore the current state of stem cell biology as it closes the gap between reality and the sci fi visions of authors such as Margaret Atwood and Philip K. Dick. Crump describes it as:

“a mad scientist type of course, where we go through some real science but also [think] about what’s the future of science.”

Don Gibbons

Museum exhibit explaining stem cell super heroes opens in Canada today, due in California in 2016

7108285_origAn international touring exhibit using super hero cells as guides to explain the many roles of stem cells in our lives opens today at the Sherbrooke Museum of Nature and Science in Canada. Its five-year tour will include further displays in Canada, the United Kingdom and three stops on California—the San Francisco Bay area, Los Angeles and San Diego—in 2016.

Super Cell logoDesigned for the general public, with a special eye to children, the exhibit uses hands-on and interactive modules to show just how important stem cells are not only to our early development but also to our daily lives. CIRM was a partner in the development of the exhibit, but the primary mover behind it has been Canada’s Stem Cell Network, and within the network, Lisa Willemse who has really pushed its two-year gestation.

The earliest steps in the development involved visits to children in schools to tease out their points of interest. In a press release she explained some of what they learned:

“How does a lizard grow a new tail? Where does disease come from? How do we start little and get big? These were the kinds of questions the kids asked us, which shows a real interest in the mysteries of the body—mysteries that are largely the domain of stem cells.”

“Much of it is easy to explain, once they understand that stem cells have the ability to make all the kinds of cells in the body. For example, you can tell them that every second, stem cells in your bone marrow make about 2 million new red blood cells. You snap your fingers, and just like that, another 2 million cells were made. Soon they all start snapping their fingers, knowing that every time they do it, something remarkable and vital to life has happened in their own body.”

In Canada, the four modules have explanations in English and French. In California, they will be in English and Spanish. In Spanish the exhibit title “Super Cells: The Power of Stem Cells” becomes Celulas Fantasticas: El Poder Del Las Celulas Madre. I love the concept of a mother cell.

Additional partners in the project included the Centre for Commercialization of Regenerative Medicine in Canada and the UK’s Cell Therapy Catapult.

Don Gibbons

Cells’ Knack for Hoarding Proteins Inadvertently Kickstarts the Aging Process

Even cells need to take out the trash—mostly damaged or abnormal proteins—in order to maintain a healthy clean environment. And scientists are now uncovering the harmful effects when cells instead begin to hoard their garbage.

Cells' penchant for hoarding proteins may spur the cellular aging process, according to new research.

Cells’ penchant for hoarding proteins may spur the cellular aging process, according to new research. [Labyrinth (1986)]

Aging, on the cellular level is—at its core—the increasing inability for cells to repair themselves over time. As cells begin to break down faster than they can be repaired, the risk of age-related diseases escalates. Cancer, heart disease and neurological conditions such as Alzheimer’s disease are some of aging’s most deadly effects.

As a result, scientists have long searched for ways to give our cells a little help and improve our quality of life as we age. For example, recent research has pointed to a connection between fasting (restricting calories) and a longer lifespan, though the molecular mechanisms behind this connection remain somewhat cryptic.

But now Dr. Daniel Gottschling, a scientist at the Fred Hutchinson Cancer Research Center and an aging expert, has made extraordinary progress toward solving some of the mysteries of aging.

In two studies published this month in the Proceedings of the National Academy of Sciences and eLife, Gottschling and colleagues discover that a particular long-lasting protein builds up over time in certain cell types, causing the buildup of a protein hoard that damages the cell beyond repair.

Clearing out the Cobwebs

Some cells, such as those that make up the skin or that reside in the gut, are continually replenished by a stockpile of adult stem cells. But other cells, such as those found in the eye and brain, last for years, decades and—in some cases—our entire lifetimes.

Within and surrounding these long-lived cells are similarly long-lived proteins which help the cell perform essential functions. For example, the lens of the human eye, which helps focus light, is made up of these proteins that arise during embryonic development and last for a lifetime.

Dr. Daniel Gottschling is looking to unlock the mysteries behind cellular aging.

Dr. Daniel Gottschling is looking to unlock the mysteries behind cellular aging. [Image courtesy of the Fred Hutchinson Cancer Research Center]

“Shortly after you’re born, that’s it, you get no more of that protein and it lives with you the rest of your life,” explained Gottschling.

As a result, if those proteins degrade and die, new ones don’t replace them—the result is the age-related disease called cataracts.

But scientists weren’t exactly sure of the relationship between these dying proteins and the onset of conditions such as cataracts, and other disease related to aging. Did these conditions occur because the proteins were dying? Or rather because the proteins were building up to toxic levels?

So Gottschling and his team set up a series of experiments to find out.

Stashing Trash

They developed a laboratory model by using yeast cells. Interestingly, yeast cells share several key properties with human stem cells, and are often the focus of early-stage research into basic, fundamental concepts of biology.

Like stem cells, yeast cells grow and divide asymmetrically. In other words, a ‘mother’ cell will produce many ‘daughter’ cells, but will itself remain intact. In general, yeast mother cells produce up to 35 daughter cells before dying—which usually takes just a few days.

 Yeast “mother” cells budding and giving birth to newborn “daughter” cells.  [Image courtesy of Dr. Kiersten Henderson / Gottschling Lab]

Yeast “mother” cells budding and giving birth to newborn “daughter” cells.
[Image courtesy of Dr. Kiersten Henderson / Gottschling Lab]

Here, the research team used a special labeling technique that marked individual proteins that exist within and surrounding these mother cells. These microscopic tracking devices then told researchers how these proteins behaved over the entire lifespan of the mother cell as it aged.

The team found a total of 135 long-lived proteins within the mother cell. But what really surprised them was what they found upon closer examination: all but 21 of these 135 proteins appeared to have no function. They appeared to be trash.

“No one’s ever seen proteins like this before [in aging],” said Nathanial Thayer, a graduate student in the Gottschling Lab and lead author of one of the studies.

Added Gottschling, “With the number of different fragments [in the mother cell], we think they’re going to cause trouble. As the daughter yeast cells grow and split off, somehow mom retains all these protein bits.”

This startling discovery opened up an entirely new set of questions, explained Gottschling.

“It’s not clear whether the mother’s trash keeper function is a selfless act designed to give her daughters the best start possible, or if she’s hanging on to them for another reason.”

Hungry, Hoarding Mother Cells

So Gottschling and his team took a closer look at one of these proteins, known as Pma1.

Recent work by the Gottschling Lab found that cells lose their acidity over time, which itself leads to the deterioration of the cells’ primary energy source. The team hypothesized that Pma1 was somehow intricately tied to corresponding levels of pH (high pH levels indicate an acidic environment, while lower pH levels signify a more basic environment).

In the second study published in eLife, led by Postdoctoral Fellow Dr. Kiersten Henderson, the team made several intriguing discoveries about the role of Pma1.

First, they uncovered a key difference between mother and daughter cells: daughter cells are born with no Pma1. As a result, they are far more acidic than their mothers. But when they ramped up Pma1 in the mother cells, the acidity levels in subsequent generations of daughter cells changed accordingly.

“When we boosted levels of the protein, daughter cells were born with Pma1 and became more basic (they had a lower pH), just like their mothers.”

Further examination uncovered the true relationship between Pma1 and these cells. At its most fundamental, Pma1 helps the mother cells eat.

“Pma1 plays a key role in cellular feeding,” said Gottschling. “The protein sits on the surface of cells and helps them take in nutrients from their environment.”

Pma1 gives the mother cell the ability to gorge herself. The more access to food she has, the easier it is for her to produce more daughter cells. By hoarding Pma1, the mother cell can churn out more offspring. Unfortunately, she is also signing her own death certificate—she’s creating a more basic environment that, in the end, proves toxic and contributes to her death.

The hoarding, it turns out, may not all be due to the mother cells’ failure to ‘take out the trash.’ Instead, she wants to keep eating and producing daughters—and hoarding Pma1 allows her to do just that.

“There’s this whole trade off of being able to divide quickly and the negative side is that the individual, the mother, does not get to live as long.”

Together, the results from these two studies provide a huge boost for researchers like Gottschling who are trying to unravel the molecular mysteries of aging. But the process is incredibly intricate, and there will likely be no one simple solution to improving quality of life as we get older.

“The whole issue of aging is so complex that we’re still laying the groundwork of possibilities of how things can go awry,” said Gottschling. “And so we’re still learning what is going on. We’re defining the aging process.”

New Cellular Tracking Device Tests Ability of Cell-Based Therapies to Reach Intended Destination

Therapies aimed at replacing damaged cells with a fresh, healthy batch hold immense promise—but there remains one major sticking point: once you have injected new, healthy cells into the patient, how do you track them and how do you ensure they do the job for which they were designed?

New tracking technique could improve researchers' ability to test potential cell therapies.

New tracking technique could improve researchers’ ability to test potential cell therapies.

Unfortunately, there’s no easy solution. The problem of tracking the movement of cells during cell therapy is that it’s hard to stay on their trail they enter the body. They can get mixed up with other, native cells, and in order to test whether the therapy is working, doctors often have to rely on taking tissue samples.

But now, scientists at the University of California, San Diego School of Medicine and the University of Pittsburgh have devised an ingenious way to keep tabs on where cells go post injection. Their findings, reported last week in the journal Magnetic Resonance in Medicine, stand to help researchers identify whether cells are arriving at the correct destination.

The research team, lead by UCSD Radiology Professor Dr. Eric Ahrens, developed something called a periflourocarbon (PFC) tracer in conjunction with MRI technology. Testing this new technology in patients receiving immune cell therapy for colorectal cancer, the team found that they were better able to track the movement of the cells than with traditional methods.

“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Ahrens in a news release. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

They tagged these cells with atoms of fluorine, a compound that normally occurs at extremely low levels. After tagging the immune cells, the researchers could then see where they went after being injected. Importantly, the team found that more than one-half of the implanted cells left the injection site and headed towards the colon. This finding marks the first time this process had been so readily visible.

Ahrens explained the technology’s potential implications:

“The imaging agent technology has been shown to be able to tag any cell type that is of interest. It is a platform imaging technology for a wide range of diseases and applications.”

A non-invasive cell tracking solution could serve as not only as an attractive alternative to the current method of tissue sampling, it could even help fast-track through regulatory hurdles new stem cell-based therapies. According to Ahrens:

“For example, new stem cell therapies can be slow to obtain regulatory approvals in part because it is difficult, if not impossible, with current approaches to verify survival and location of transplanted cells…. Tools that allow the investigator to gain a ‘richer’ data set from individual patients mean it may be possible to reduce patient numbers enrolled in a trial, thus reducing total trial cost.”

What are the ways scientists see stem cells in the body? Check out our Spotlight Video on Magnetic Particle Imaging.

New Videos: Living with Crohn’s Disease and Working Towards a Stem Cell Therapy

Note: the two videos below are also available on our website

She doesn’t want your sympathy. She doesn’t want your admiration. She just wants your understanding.

Rachel Bonner, a sixteen-year-old high school student and founder of the Hope for Crohn’s charity, spoke to the CIRM governing Board on September 10th about what it’s like living with Crohn’s disease. In the eight years since her diagnosis, Rachel has come a long way in talking publicly about her condition:

“I never thought I’d stand up here and admit to wearing a diaper while being in middle school. But Crohn’s turns from a secret struggle to something I want to share with other people. And ultimately have others understand the life of a Crohn’s patient just a bit more. “

Crohn’s disease is a type of inflammatory bowel disease (IBD) in which the intestines are chronically inflamed. Symptoms of Crohn’s include a frequent need to pass bowel movements, constant diarrhea, rectal bleeding, fatigue and loss of appetite.

In a healthy individual, the friendly bacteria living in the gut are ignored by the immune system. But in the case of IBD, the immune cells attack these bacteria as foreign invaders, causing an inflammatory response. The sustained inflammation eventually damages the gut wall causing the symptoms of IBD.

Current therapies for IBD focus solely on treating the inflammation. Dr. Ophir Klein, a CIRM grantee and UCSF researcher, also spoke to the governing Board and described another treatment avenue:

“There’s another component that’s been under-explored and potentially has a lot of impact therapeutically which is the regenerative aspects of the condition because after the inflammation occurs in the gut, the gut needs to heal, and that healing comes from stem cells. “

In his presentation to the Board, Dr. Klein detailed his lab’s work to understand how stem cells regulate the healing of the intestine and to eventually find cures for IBD.

Although Rachel and her doctors have found a treatment sweet spot, which has kept her Crohn’s at bay, she still holds out hope that a cure, perhaps from a stem-cell based therapy, is not too far away:

“Everyday I go to sleep hoping that this treatment sweet spot will work until they find a cure”