Cranking up stem cell production for when therapies are approved for widespread use

Getting a cell therapy from the research bench to patients requires leaping many hurdles. Perhaps two of the highest arise when proving the potential therapy is safe enough to begin clinical trials and then when scaling up production to meet the demand of thousands of patients.

Scale up to producing the 100s of billions of cells needed to treat large groups of patients could be a roadblock for therapies.

Scale up to producing the 100s of billions of cells needed to treat large groups of patients could be a roadblock for therapies.

An even dozen CIRM-funded projects have made it over the first hurdle. No doubt those teams have begun planning for that last big jump, but in reality, in most cases the processes needed to make cells for a dozen or a few dozen patients in early trials don’t generally scale to the thousands. When you look at the number of cells needed for one heart repair, for example, around five billion, the numbers are mind bending.

Many organizations focus on this issue as their main goal looking for platforms that can help scale up production for cell therapies across many different diseases. A team at the University of Nottingham in England recently reported results from a $3.6 million project that seems to have created a sizeable piece of the solution. They developed a fully synthetic substrate, which has no chance for contamination, that can grow cells by the billion, both stem cells and the more mature cells normally desired for transplant into patients.

“The possibilities for regenerative medicine are still being researched in the form of clinical trials,” said the project leader Morgan Alexander in a university press release posted by ScienceDaily. “What we are doing here is paving the way for the manufacture of stem cells in large numbers when those therapies are proved to be safe and effective.”

The research team used a high throughput lab technique to test many materials until they finally arrived at the one they reported in the journal Advance Materials.

New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.

I Sing the Bioelectric: Long-Distance Electrical Signals Guide Cell Growth and Repair

Genes turn on, and genes turn off. Again and again, the genes that together comprise the human genome receive electrical signals that can direct when they should be active—and when they should be dormant. This intricate pattern of signals is a part of what guides an embryonic stem cell to grow and mature into any one of the many types of cells that make up the human body.

Bioelectric signals sent between cells—even cells at great distance from each other—have been found to carry important instructions relating to the growth, development and repair of organs such as the brain.

Bioelectric signals sent between cells—even cells at great distance from each other—have been found to carry important instructions relating to the growth, development and repair of organs such as the brain.

These electrical signals that guide cell growth have long been described as molecular ‘switches.’ But now, scientists at Tufts University have decoded these electrical signals—and discovered that they are far more complex than we had ever imagined.

Reporting in today’s issue of the Journal of Neuroscience, lead author Michael Levin and his Tufts research team have mapped the electrical signals transmitted between cells during development, and found that not only do these signals direct when a gene should be switched on, they also carry their own set of instructions, crucial to cellular development. Using the example of brain formation, Levin explained in today’s news release:

“We’ve found that cells communicate, even across long distances in the embryo, using bioelectrical signals, and they use this information to know where to form a brain and how big that brain should be. The signals are not just necessary for normal development; they are instructive.”

Instead of a molecular switchboard, an analogy that some have used to describe these bioelectrical signals, Levin likened the system to a computer. The signals themselves act like software programs, delivering instructions and information between cells at precisely the right time—even cells at great distance from one another.

Using tadpole embryos as a model, the team identified that the pattern of changes in voltage levels between cell membranes, called cellular resting potential, is the source of these bioelectrical signals, which are crucial to cellular development.

Specifically, the team mapped the changing voltage levels in embryonic stem cells in regards to the formation of the brain. In addition to discovering that these bioelectric signals instruct the formation of organs such as the brain, their discovery also hints at how scientists could manipulate these signals to repair tissues or organs that have been damaged—or even to grow new, healthy tissues.

“This latest research also demonstrated molecular techniques for ‘hijacking’ this bioelectric communication to force the body to make new brain tissue at other locations and to fix genetic defects that cause brain malformation,” Levin explained. “This means we may be able to induce growth of new brain tissue to address birth defects or injury, which is very exciting for regenerative medicine.”

In addition, the authors argue that modifying the bioelectrical signals to generate tissue—rather than modifying the genes themselves—may reduce the risk of adverse effects that may crop up by modifying genes directly.

While it’s early days for this work, Levin and his team foresee ways to apply this knowledge directly to medicine, for example by developing electricity-modulating drugs—which they call ‘electroceuticals’—that can repair damaged or defective tissue, and induce tissue growth.

Stay on Target: Scientists Create Chemical ‘Homing Devices’ that Guide Stem Cells to Final Destination

When injecting stem cells into a patient, how do the cells know where to go? How do they know to travel to a specific damage site, without getting distracted along the way?

Scientists are now discovering that, in some cases they do but in many cases, they don’t. So engineers have found a way to give stem cells a little help.

As reported in today’s Cell Reports, engineers at Brigham and Women’s Hospital (BWH) in Boston, along with scientists at the pharmaceutical company Sanofi, have identified a suite of chemical compounds that can help the stem cells find their way.

Researchers identified a small molecule that can be used to program stem cells (blue and green) to home in on sites of damage. [Credit: Oren Levy, Brigham and Women's Hospital]

Researchers identified a small molecule that can be used to program stem cells (blue and green) to home in on sites of damage. [Credit: Oren Levy, Brigham and Women’s Hospital]

“There are all kinds of techniques and tools that can be used to manipulate cells outside the body and get them into almost anything we want, but once we transplant cells we lose complete control over them,” said Jeff Karp, the paper’s co-senior author, in a news release, highlighting just how difficult it is to make sure the stem cells reach their destination.

So, Karp and his team—in collaboration with Sanofi—began to screen thousands of chemical compounds, known as small molecules, that they could physically attach to the stem cells prior to injection and that could guide the cells to the appropriate site of damage. Not unlike a molecular ‘GPS.’

Starting with more than 9,000 compounds, the Sanofi team narrowed down the candidates to just six. They then used a microfluidic device—a microscope slide with tiny glass channels designed to mimic human blood vessels. Stem cells pretreated with the compound Ro-31-8425 (one of the most promising of the six) stuck to the sides. An indication, says the team, Ro-31-8425 might help stem cells home in on their target.

But how would these pre-treated cells fare in animal models? To find out, Karp enlisted the help of Charles Lin, an expert in optical imaging at Massachusetts General Hospital. First, the team injected the pre-treated cells into mouse models each containing an inflamed ear. Then, using Lin’s optical imaging techniques, they tracked the cells’ journey. Much to their excitement, the cells went immediately to the site of inflammation—and then they began to repair the damage.

According to Oren Levy, the study’s co-first author, these results are especially encouraging because they point to how doctors may someday soon deliver much-needed stem cell therapies to patients:

“There’s a great need to develop strategies that improve the clinical impact of cell-based therapies. If you can create an engineering strategy that is safe, cost effective and simple to apply, that’s exactly what we need to achieve the promise of cell-based therapy.”

‘STARS’ Help Scientists Control Genetic On/Off Switch

All life on Earth relies, ultimately, on the delicate coordination of switches. During development, these switches turn genes on—or keep them off—at precise intervals, controlling the complex processes that guide the growth of the embryo, cell by cell, as it matures from a collection of stem cells into a living, breathing organism.

Scientists have found a new way to control genetic switches.

Scientists have found a new way to control genetic switches.

If you control the switch, you could theoretically control some of life’s most fundamental processes.

Which is precisely what scientists at Cornell University are attempting to do.

Reporting in today’s issue of Nature Chemical Biology, synthetic biologists have developed a new method of directing these switches—a feat that could revolutionize the field of genetic engineering.

At the heart of the team’s discovery is a tiny molecule called RNA. A more simplified version of its cousin, DNA, RNA normally serves as a liaison—translating the genetic information housed in DNA into the proteins that together make up each and every cell in the body.

In nature, RNA does not have the ability to ‘turn on’ a gene at will. So the Cornell team, led by Julius Lucks, made a new kind of RNA that did.

They engineered a new type of RNA that they are calling Small Transcription Activating RNAs, or STARS, that can serve as a kind of artificial switch. In laboratory experiments, Lucks and his team showed that they could control how and when a gene was switched on by physically placing the STARS system in front of it. As Lucks explained in a news release:

“RNA is like a molecular puzzle, a crazy Rubik’s cube that has to be unlocked in order to do different things. We’ve figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock.”

RNA is an attractive molecule to manipulate because it is so simple, says Lucks, much simpler than proteins. Many efforts aimed at protein manipulation have failed, due to the sheer complexity of these molecules. But by downshifting into the simpler, more manageable RNA molecules, Lucks argues that greater strides can be made in the field of synthetic biology and genetic engineering.

“This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well,” said Lucks.

In the future, Lucks envisions a system based solely on RNA that has the capability to manipulate genetic switches to better understand fundamental processes that guide the healthy development of a cell—and provide clues to what happens when those processes go awry.

Stem Cell Stories that Caught Your Eye: The Most Popular Stem Cellar Stories of 2014

2014 marked an extraordinary year for regenerative medicine and for CIRM. We welcomed a new president, several of our research programs have moved into clinical trials—and our goal of accelerating treatments for patients in need is within our grasp.

As we look back we’d like to revisit The Stem Cellar’s ten most popular stories of 2014. We hope you enjoyed reading them as much as we did reporting them. And from all of us here at the Stem Cell Agency we wish you a Happy Holidays and New Year.

10. UCSD Team Launches CIRM-Funded Trial to Test Safety of New Leukemia Drug

9. Creating a Genetic Model for Autism, with a Little Help from the Tooth Fairy

8. A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

7. CIRM funded therapy for type 1 diabetes gets FDA approval for clinical trial

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

5. Creativity Program Students Reach New Heights with Stem Cell-Themed Rendition of “Let it Go”

4. Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

3. Meet the Stem Cell Agency President C. Randal Mills

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

1. UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

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.