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Reported January 18, 2013

Organ Transplants: Making Old Organs New Again--In-Depth Doctor's Interview

Dr. Roger De Filippo, principal investigator at The Saban Research Institute of Children’s Hospital Los Angeles, talks about building organs in the laboratory.

So you see firsthand how a kidney and the failure of kidneys can affect someone from birth?

Dr. De Filippo: Yes. We deal with a lot of congenital conditions. Kids that are born with conditions that would mean significant compromise to their kidney function. We operate on a lot of children that have conditions of the kidney that require extensive reconstruction. It is a part of what we do every day.

A lot of kids come through your hospital that would really benefit from kidney transplants and have to stay on the list for a long time. Do you see their health fail? 

Dr. De Filippo: There are a lot of patients today waiting on a transplant list for kidney transplant. While they are waiting, they require dialysis. Having research that could potentially offer them other alternatives is worth pursuing.

And part of that is regenerative medicine right?

Dr. De Filippo: Certainly; regenerative medicine, bioengineering, tissue engineering, all of that is an important aspect of the work that we are doing in the laboratory.

Can you tell me a little bit about that the kidney that you are building in the lab?

Dr. De Filippo: When we first started here, nearly 10 years ago, one of our focuses was regenerating kidneys in the laboratory. So we were actually able to do that with kidneys on a small scale, using stem cells that we were able to retrieve from amniotic fluid. Amniotic fluid is a very good source of stem cells and other cells that lend themselves to regenerative medicine, tissue engineering, and bioengineering. That was actually one of our first projects in looking at our ability to use concepts in embryology and developmental biology to reconstruct these kidneys. We were actually able to insert these cells into small developing kidneys and what we found was that these cells were able to regenerate tissue and would become part of the kidney.

Was that a surprise? 

Dr. De Filippo: Well it had never been done before. We were hypothetically thinking that that would happen, but it certainly was a pleasant surprise to see it occur.

Is it just regenerating cells in your own kidney?

Dr. De Filippo: We have 2 basic lines of research in our laboratory; one very classic tissue engineering line where we are building kidneys with scaffolds using regenerative cells. These are the cells that were destined to become various parts of the kidney that we were able to isolate from amniotic fluid. We are also using a cell therapy, where we are able to inject these cells into damaged kidneys or kidneys that would eventually succumb to their disease and fail, and we are able to stave off organ failure.

Does it stop the disease in its progression? What types of diseases are you talking about? 

Dr. De Filippo: We have a model right now for chronic kidney disease, which we are working on. We are replicating conditions that in a human would require dialysis. What we are finding is using this cell therapy; we are actually able to slow down the progression of the disease pretty significantly. 

How much?

Dr. De Filippo: We have some models right now that have received recurrent therapies and that we have been able to basically preserve their renal function to where they are not having any signs or any significant signs, of end stage disease in other words.

Does that suggest that in the future, using these therapies, someone could be able to get off of dialysis?

Dr. De Filippo: That is certainly our hope to delay the need for dialysis quite significantly. That alone would be a very significant improvement over what we have now. The longer you can delay dialysis, the better it is for the patient. An analogy could be someone taking insulin for diabetes. If we could give our patients a therapy that would be similar to that, so that they would not succumb to their disease so early; that certainly would allow them to live a normal life with their disease.

Do you see these future therapies cutting down on the need for transplant?

Dr. De Filippo: Our hope would be that we would have fewer patients on a transplant list. That would mitigate the pressure that is on that list right now because you have a lot of patients and very few organs available.

Why use amniotic stem cells instead of the more well known, but controversial, embryonic stem cells? 

Dr. De Filippo: Well, we have been working with this source of cells for quite some time, over 10 years. There are a lot of advantages with amniotic fluid stem cells; they are cells that are easily retrievable. They present very little in the way of harm for either the baby or the mother. They are cells that you can acquire in very large number, so for regenerative medicine purposes, or for tissue engineering purposes, that is very appealing because you need a lot of cells to basically build organs in the laboratory and you need a lot of cells for cell therapy. Amnionic stem cells don’t form tumors like your classic embryonic stem cells. They also don’t come with a lot of the ethical concerns associated with perhaps other embryonic stem cells lines. Yet, they are what we call pleury-potent so they can be differentiated into a variety of cell types and, therefore, be used for a variety of purposes. For these reasons, they are very appealing to bioengineers, tissue engineers, and regenerative medicine scientists.

Do you think it is too early for parents to start thinking about embryonic stem cell banks?

Dr. De Filippo: Not at all. This is a very exciting time for stem cell biologists and scientists everywhere. It is also interesting to think in terms of parents banking stem cells. Currently, parents are banking of cord blood and, so far, that is just a single stem cell type. As clinicians, we are faced with the fact that one cell type is not going to be ideal for everything we may need a variety of cell types to have at our disposable to treat diseases in a child’s future.

Can you list off 4 or 5 different kidney diseases that you are specifically working on?

Dr. De Filippo:  We are working on acute kidney disease like acute tubular necrosis. We have a model for diabetic nephropathy, kidney disease related to diabetes. We are working on an Alport model in the laboratory that is a genetic disease that is a form of chronic kidney disease and ultimately can lead to kidney failure. Those are the 3 main models that we are working on right now. 

How long until you begin treating patients in clinical trials?

Dr. De Filippo: We are very hopeful that some of our cell therapy work could be realized within the next 5 years. I think that is certainly a very realistic goal of ours. The cell therapy work that we are doing for chronic kidney disease could be in patients in the next 5 years. I think we have some very good data to support this projection and we are doing our best to make it happen.

Do you think the controversy surrounding stem cells is holding scientists back here in America compared to other countries?

Dr. De Filippo: What makes it great to work in a country like ours is that we can have those discussions and address the, issues.  It allows us, as scientists, the opportunity to educate our colleagues and educate the population. I don’t think those are actually apprehending our discussions create obstacles in the long run. That being said, there are also alternative sources of stem cells, such as the amniotic fluid stem cells we are using in our lab, that tend to avoid many of the ethical issues.

 

END OF INTERVIEW

This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.

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If you would like more information, please contact:

 

Ellin Kavanagh
Senior Public Information Officer, Research
Marketing Communications Department
Children’s Hospital, Los Angeles
(323) 361-8505
ekavanagh@chla.usc.edu

 

 

To read the full report, Making Old Organs New Again!, click here.

 

 

 

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