April 20, 2012
NIH Podcast Episode #0157
Balintfy: Welcome to episode 157 of NIH Research Radio. NIH Research Radio bringing you news and information about the ongoing medical research at the National Institutes of Health – NIH . . . Turning Discovery Into Health®. I'm your host Joe Balintfy, and coming up in this episode a series of stories from the NIH Clinical Center.
“The Clinical Center at NIH in general is doing research on stem cell therapy and research shows that less than 3 percent of stem cells actually make it to the right place.”
Just a small sample of the work being done at America’s Research Hospital. Also, how you can get involved: an interview about clinical research trials and participating in that research. But first, this news update. Here’s Craig Fritz.
Fritz: Scientists have identified which strains of a parasite that causes toxoplasmosis, are most strongly associated with premature births and severe birth defects in the United States. Researchers used a new blood test developed by scientists at NIH, to pinpoint parasite strains that children acquire while in the womb. Pregnant women can become infected with the parasite through contact with infected cat feces or by eating undercooked meat. Infected women may miscarry, give birth prematurely, or have babies with eye or brain damage. The new test improves upon older tests because it can distinguish infecting strains from one another. At least 15 distinct parasite strain types have been found throughout the world, though a strain known as type II is most common and can be distinguished from all other strains. Using the new test, the researchers found infections in 183 of the mother-child pairs in the study. Results showed that other strain parasites were more likely to be associated with premature birth and severe manifestations of disease in infants than those infected by type II parasites. The researchers note that the association is not absolute, and that mild, moderate or severe disease can result regardless of the infecting strain.
For this NIH news update – I’m Craig Fritz.
Balintfy: News updates are compiled from information at www.nih.gov/news. Coming up, the inside scoop on clinical research trials, plus tracking, targeting and transfusing cells to treat disease. That’s next on NIH Research Radio.
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NIH researchers discover method to tag transplanted cells for tracking by MRI
Balintfy: In the news update of our last episode, Craig talked about how an NIH study has shown that a new technique for improving delivery of stem cells may lead to better and faster tissue repair. We’re turning now to Ellen Crown at Clinical Center Radio for a series she produced related to this topic. Ellen.
Crown: Thanks Joe. Well, the human body is made up of trillions of cells working together to keep the organs and systems healthy and strong. But when disease invades or an injury occurs, one option is to introduce new cells to try to strengthen the body's army of cells and help the body regenerate and heal. But not all transplanted cells reach their target. Dr. Joseph Frank, chief of the Clinical Center's Radiology and Imaging Sciences Laboratory of Diagnostic Radiology Research explains:
Frank: A large majority of the cells that you end up giving to the person don't make it to where you want them to go because they die or because they are going into a different environment. Potentially, only 3 percent of those cells will actually get to be alive at, say, three days later.
Crown: Regenerative medicine and treatments such as cell therapy hold great promise. But Dr. Frank says cell tracking is crucial to better understand optimal dosing levels and frequency of treatments. Cell tracking is currently done with radioisotopes or reporter genes. But these methods have limitations and risks for patients. Dr. Frank and his team have developed a new method to label transplanted cells so they can be tracked by magnetic resonance imaging, or MRI. Their method involves tagging the transplanted cells with three medications that are already approved by the Food and Drug Administration -- heparin, protamine, and ferumoxytol.
Frank: The difference here and the reason why this technology is interesting is that we've used FDA-approved product. You can actually get them from a pharmacy and mix them together. They self-assemble. They come together on their own. Then essentially can be used to magnetically tag the cells. Then with MRI you can follow where they go.
Crown: Dr. Frank and his team hope to soon test this new cell tracking method in patients with brain tumors.
Ultrasound used to target stem cell therapy
Balintfy: Thanks Ellen. So once researchers see where the cells are going, the next step is to make sure they’re actually getting to the right place. So your next report is about how ultrasounds are used to target stem cell therapy. Can you explain that?
Crown: That’s right. NIH researchers have been carefully reviewing stem cell therapy as an alternative method for injuries and disease treatment. Part of this research includes the study of bone marrow stromal cells. These cells are believed to stimulate new bone growth and help regulate the immune system. But as with all cell therapy, the tracking and targeted delivery of the transfused cells have been critical pieces of a puzzle. Dr. Joseph Frank, chief of the Clinical Center’s Radiology and Imaging Sciences Laboratory of Diagnostic Radiology Research, recently announced that he and his team have developed a new method to label transplanted cells so they can be tracked by magnetic resonance imaging, or MRI. Now he has unveiled a new discovery – a noninvasive method of using pulsed, focused ultrasound to precisely target stem cell delivery.
Frank: The technique is essentially with a noninvasive approach. We’re just scanning across the skin in an area, directing it where we want to. We can put multiple pulses in the area that we want and change the microenvironment of the tissue. Essentially, we’re developing what we could commonly call a molecular zip code for that cell to be able to home to that area and then migrate across.
Crown: Dr. Frank explains that the ultrasound works by causing the tissue to temporarily release natural chemicals, such as cytokines, integrins, and growth factors, to which the cells are attracted. It doesn’t hurt the tissue and, in fact, the tissue is only affected for a short period of time – about 24-36 hours. This may make is feasible to do multiple applications over a relatively short period of time.
Frank: So the concept is that we can come back multiple times. And, in fact, when we do daily combinations of the pulsed focused ultrasound with the stem cell infusion, we actually have highly significant differences in the number of cells after three days compared to just a single course of stem cells.
Crown: Traditional non-invasive methods of cell therapy typically have less than 3 percent success rate of the transplanted cells reaching their target. Dr. Frank’s study showed that using pulsed, focused ultrasound prior to cell therapy multiplied cell delivery up to eight to 10 times that of traditional methods. However, Dr. Frank explains that more cells may not be better. Researchers are still trying to better understand issues such as optional dosing and timing.
Frank: You can always put more cells in by putting a catheter into a vessel and directing it the area that you want or directly injecting it. The concept now is that I can noninvasively without damaging the tissue put more cells in the tissue. And is that going to be better for repair? Is the going to be better for regenerative medicine?
Balintfy: Again that was Dr. Joseph Frank at the NIH Clinical Center. And this is the story that Craig reported in last week’s news headlines.
NIH Clinical Center transfuses bone marrow stromal cells to first study participant
Balintfy: Ellen, I thought it would make sense to explain a little bit more about what bone marrow stromal cells are. They’re cells that are found in the bone marrow but do not develop into blood cells. That’s typically what we think of when we hear about bone marrow, that’s where red blood cells are made.
Crow: That’s right.
Balintfy: Instead, they help support, nourish, and regulate the blood-forming cells.
Crown: So we have some news actually at the NIH Clinical Center. We treated our first study participant with bone marrow stromal cells, which researchers believe may help to regulate the patient's immune system. Dr. David Stroncek, chief of the Department of Transfusion Medicine's Cell Processing Section says:
Stroncek: We've been working on this project with my lab, and with clinical investigators at the NIH and with laboratory researchers at the NIH for over three years, both to develop the laboratory procedures, the good manufacturing procedures to grow these cells, and the clinical protocols to treat the patients.
Crown: The study volunteer who received the bone marrow stromal cells is currently enrolled in a protocol conducted by the National Heart, Lung and Blood Institute. The study volunteer has graft-versus-host disease, a complication that can occur after a stem cell or bone marrow transplant in which the donor immune system attacks the transplant recipient's body. Researchers hope the bone marrow stromal cells will suppress the patient's immune system.
Healthy volunteers provided the cells for this study. The cell processing team starts with a small amount of cells retrieved from a small bone marrow donation. The rest are grown over a one-month period.
Stroncek: We start with a small bone marrow aspirate that really has very few of these stromal cells and we culture them in small flasks. They gradually grow, and as they grow we have to transfer the culture into bigger and bigger flasks. Finally, we start out with maybe a few flasks with maybe 100 milliliters of media that the cells are growing in. By the time the 28 days are over, we have eight very large flasks, which are called cell factories, with about 10 liters of media. So the cells have expanded thousands-fold.
Crown: The study will include giving patients a series of three transfusions throughout a three-week period. While research investigators hope to learn more about bone marrow stromal cells, the transfusion medicine experts will learn more about the characteristics of the cells and the best processing methods.
Stroncek: Should we give them more often than three times? Should we give them a higher cell dose? We also think there is going to be some variability in the cells with a lot of the cells we use. So we want to try to figure out what the characteristics of the cells that we give are the most important. Then what we would like to do then is to modify the way we give cells down the line, so we can make the best possible cell that is the most effective in treating patients.
Balintfy: Again that’s Dr. David Stroncek at the NIH Clinical Center. Ellen these three reports from you, although from different programs and studies, have a similar theme. How would you summarize them so listeners can make the connection.
Crown: Well I think in the first story, in the story about MRI tracking, we learn more about a method for finding out if the stem cells are actually making it to their targeted area. Which is very important as we know because less than 3 percent of stem cells actually make it to the place that we want them to make it to.
In the story about using ultra sound to target stem cell therapy we find out about new methods for trying to be more effective for our stem cell delivery.
And then with the story about transfusing bone marrow stromal cells we find out how this is being applied to patients. Which is great because that is one step further applying it to a clinical setting hopefully in the future.
Balintfy: I think it’s a great series because it goes from imaging research to testing research, and ultimately applying research. If listeners what to hear more about these studies or tune in to more NIH Clinical Center Radio, where can they find you?
Crown: They can go to our website and there is all kinds of information about our research and they can listen to more Clinical Center podcasts right from our home page.
Balintfy: And that homepage is clinicalcenter.nih.gov. Thank you very much Ellen.
Crown: Thank you Joe.
Balintfy: That’s Ellen Crown at NIH Clinical Center Radio. And coming up here on NIH Research Radio, more about clinical trials. That’s next.
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Clinical research trials
Balintfy: You’ve been hearing us talk about the Clinical Center here on NIH Research Radio. Some quick background: the NIH Clinical Center is the research hospital here on the NIH campus. It is the world’s largest hospital devoted exclusively to clinical research, meaning it is dedicated to rapidly taking scientific observations and laboratory discoveries into new approaches for diagnosing, treating and preventing disease. Each year, the Clinical Center cares for about 6,000 inpatients and 10,000 outpatients – all of whom are participants in clinical research studies.
We’re talking now with Dinora Dominguez. She is Chief of the Patient Recruitment and Public Liaison Office for the NIH Clinical Center. And, to get the big picture Dinora, how would you define research studies?
Dominguez: So research studies if you will is sort of the umbrella because research studies then is divided then into clinical trials with individual patients. A research study can be any type of research that's being done in the outside world and that could be sociology, anthropology, any type of medical, of course, and device research study. But a clinical trial is what we predominantly concentrate on and that is where you are dealing with individuals, with human beings, and they are participating in a study related to a very specific question that an investigator or their team wants to find the answer to.
Balintfy: And what kind of clinical trials are there?
Dominguez: So there are lots of different clinical trials. There could be a clinical trial where it's just a natural history study which is very specific to us at the Clinical Center at the NIH, and that is looking at somebody through the years and what's the natural course if you will of the condition, of the disease, the diagnosis that they are looking at. Then there are clinical trials that actually start from Phase Zero all the way through Phase 4.
Balintfy: Each phase has a different purpose and helps researchers answer different questions. For example, phase I is designed to evaluate safety and identify side effects; phase II is to determine effectiveness and further check safety; phase III is to confirm effectiveness, monitor side effects and compare with a standard or equivalent treatment; and phase IV is for continued safety tracking and optimal use. And Dinora these trials are typically looking at a drug or device, right?
Dominguez: So the Phase Zero through 4, really they are looking at a medication or a device or a different -- or a medication that's already been approved for one condition, but now the research has shown and the bench has shown that this could possibly be of benefit for another condition.
Balintfy: Now when you say bench, you’re not talking about a park bench where researchers might be sitting, right?
Dominguez: Right. So that is the term that we use. It's not a bench under the cherry blossoms which happened to be beautiful right now. No, the bench is the concept that they are in a laboratory and they are working in the lab looking at what their particular hypothesis is.
Balintfy: This is where we get the saying, from bench to bedside, meaning we take a discovery in the lab and apply it to a patient. And there are different types of researchers that may be involved in a study. Who are those people?
Dominguez: So the research team, if you will, starts off with the principal investigator. The principal investigator may have associate investigators and then they have research coordinators, research nurses, and specific consultants. If it's a study that needs to look at dietary intake and needs, so you may have specialists from the area of dieticians, nutritionists, exercise physiologists or you may have different cardiologists. I mean there's even to administer testing for mental health studies. Those individuals need to be trained. So it's really a team effort.
Balintfy: But an integral part of the team is the patient or the volunteer. There have to be participants in the study, right?
Dominguez: Oh, absolutely. We can have the absolute best thoughts and protocols and clinical trials in place; but if we don't have the participants, we're not going to go anywhere and that's the key of the relationship that we have that it really is a partnership. It's a partnership between the research team headed by the principal investigator and the participants. Whether the participants are individuals with medical conditions or whether they are individuals that are healthy, we need them and they need us to move science forward.
Balintfy: You mentioned another term I hear a lot, but maybe not everyone is familiar with. What’s a protocol?
Dominguez: So a protocol is where the investigator comes up with an idea and comes up with a concept of “Okay, this is what either I believe is going to happen because of all the research that I've done at the bench, and I think that now if I take this to humans this is what's going to happen. These are the steps that I need to take; these are the tests that I need to run on these individuals; these are the results that I'm hoping for; these are the results I don't want to see” lots of other pieces to it, citations and reference checks and so forth. But in terms of for the patient, that’s really what a protocol is.
Balintfy: So the protocol is like a roadmap – it’s the outline and description of expectations.
Dominguez: Right, right.
Balintfy: But back to participating in a clinical research trial. I’ll be doing that myself later this summer, what do you think is most important to know about clinical trials?
Dominguez: Everyone has the right to say no. I think that a lot of individuals through the years I've encountered, I feel like once they have committed that that's it, and certainly it's very important to keep the individual enrolled in the study. But there is the right at any point that the individual can say, “No, I'm not interested in pursuing. I'm not interested in X or Y.”
The other piece is that informed consent is a process; that it's not just that one time that you sign a document and then you're done and that's it, but that it's really a process that you want to be involved in and you want to have conversations with all of the individuals that are providing research care for you.
And I think also that it's necessary for all of us to participate, whether it's as a healthy, whether it's as an individual with a specific medical condition or diagnosis because it's really the way that we can advance science. There is really no other way around it but we need to test these ideas of the individuals that have put years and years of their life into “I think that this is what's needed to go to the next phase.” So I would say those are probably the three biggest issues.
Balintfy: What kind of diseases are being studied and who are the people that are volunteering?
Dominguez: We have studies that are for common conditions and we have studies that are for very rare conditions where we're the only ones that might see the five individuals that have the condition in the world. And we have studies for individuals that still don't really know what their diagnosis may be. So we have that entire program that we work with as well.
And individuals will come and they may very well be in a study that provides them some type of hope in the sense of immediate hope of a studied medication that we're looking at. But many of them come and really it's to help us advance science. There is nothing in it for them.
Balintfy: Thank you Dinora Dominguez at the Patient Recruitment and Public Liaison Office for the NIH Clinical Center. We’ll hear more from her later in the year. In the mean time if you would like more information about participating in a clinical research trial, visit the website clinicalresearchtrials.nih.gov. Or you can find information about clinical research trials that are currently recruiting by calling 1-800-411-1222 or visiting the website, clinicaltrials.gov.
Balintfy: For now, that’s it for this episode of NIH Research Radio. Please join us again on Friday, May 4th when our next edition will be available. We’ll be discussing how May is Healthy Vision Month. If you have any questions or comments about this program, or have story suggestions for a future episode, please let me know. Send an email to NIHRadio@mail.nih.gov. Also, please consider following NIH Radio via Twitter @NIHRadio, or on Facebook. Until next time, I'm your host, Joe Balintfy. Thanks for listening.
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