Transcript
Narrator:
The Diabetes Research Institute presents a series of reports on the latest progress in cure-focused research – promising discoveries aimed at restoring natural insulin production in those living with diabetes.
Reporter:
Type 1 diabetes destroys the cells in the pancreas which produce insulin.
At the Diabetes Research Institute, scientists are trying to find ways to restore that insulin production.
They believe stem cells could be the answer. Juan Domínguez-Bendala, Ph.D., is Director of Stem Cell Development for Translational Research at the DRI.
Dominguez-Bendala:
“Stem cells have two unique properties. One of them is that they keep dividing all the time so you can get them to expand in very significant numbers. So in a very short period of time you can get as many as you need to treat all the patients that you may want to treat. The other property that they have is that they are like a blank slate. They are naïve. They are simply waiting for instructions to become something. They are waiting to be programmed to become one tissue or another."
Reporter:
Dominguez-Bendala and his team are trying to program them to become islet cells – which produce insulin. If successful, scientists could place the islets in patients suffering from type 1 diabetes.
But, Dominguez-Bendala says, if stem cells were left to develop on their own, less than 1% would become islets.
Dominguez-Bendala:
“So our challenge is to force them, to drive them into that particular direction, which is not their preferred choice, so to speak.”
Reporter:
It’s a step-by-step process, he says – five steps in all.
Dominguez-Bendala:
“And we know after many years of studies, we know what genes are activated in each one of these steps, so we can try to sequentially trigger the activation of these genes.
“We have our very nice road map of all the genes and all the steps that are involved in the process and it’s only a matter of mimicking it in vitro or in a Petri dish, which is challenging.”
Reporter:
Challenging, because in a Petri dish, cells are removed from the complex structure they would normally grow in – a structure in which neighboring cells send important signals to the stem cell.
In the Petri dish, there are no neighboring cells. So, Dominguez-Bendala and his team have developed groundbreaking technology to circumvent that problem. They’re placing proteins into the stem cells. These proteins will act as switches, driving stem cells along each one of the developmental milestones that lead to beta cells
Dominguez-Bendala:
“You simply put the proteins in the culture medium and 100% of the cells will be receiving that protein and we have seen that by putting this protein into embryonic stem cells or other stem cells, they are actually driven towards a pancreatic fate
Reporter:
Dominguez-Bendala says of the five steps required to turn a stem cell into an islet cell, the DRI has accomplished three, and is working on the remaining two.
He says the DRI has dramatically improved the process by inventing a system to deliver more oxygen to the cells as they develop. Islets require a lot of oxygen. Even though they make up less than 1% of the total weight of a pancreas, they receive more than 25% of the organ’s oxygen.
The DRI invention provides oxygen to the cells both from above – and below. A so-called “oxygen sandwich.”
Dominguez-Bendala:
“Typically, when you culture cells you put them into a Petri dish, which is a plastic thing and then you cover them in culture medium. The oxygen is the oxygen that we breathe and it diffuses through the culture medium into the cells. We have found that this very inefficient and cells are very low in oxygen. Among other things because they are sitting atop plastic and plastic is completely impermeable to oxygen. We have invented this platform in which the bottom has been replaced, instead of being plastic,is a membrane that is made of a compound with a very high affinity for oxygen. So in fact, oxygen has been delivered to the cells both from the top and the bottom.”
Reporter:
And, he says, the results have been impressive.
Dominguez-Bendala:
“We took the stem cells and just by putting them in there, without any, adding any protein, any growth factor, doing anything to them, without doing anything to them, we saw that these cells started to become insulin positive cells with a much higher frequency. And in fact we saw that some of the cells started to express insulin at a 100 fold the usual levels that we saw in the standard culture vessels.”
Reporter:
Dominguez-Bendala says that until recently, most research has focused on embryonic stem cells. But now the DRI is studying other types – such as umbilical cord and amniotic stem cells.
He says umbilical cord cells could hold more potential than originally thought – and that a specific sub-population of cord cells could, in fact, turn into insulin producing cells.
Dominguez-Bendala:
“If that was the case, then we have another source which is less controversial from many points of views um, than embryonic stem cells and is easily accessible. We can get them all the time from any delivery room in any hospital of the country.”
Reporter:
He says the challenge with cord cells is that they do not grow as quickly or as easily as embryonic stem cells.
As for amniotic stem cells, the DRI is collaborating with Dr. Anthony Atala of Wake Forest University, who found these cells have the ability to become many different cell types.
Dominguez-Bendala:
“To date, we still don’t have evidence that they can become pancreatic, but what we know is that we can expand them exactly as we do expand embryonic stem cells so they are very easy to work with and they may have the potential to become pancreatic. So we are very excited about that possibility of using them, but this is brand new.”
Reporter:
As Dominguez-Bendala and his team pursue these exciting possibilities, he says he’s grateful he’s able to do it at the DRI.
Dominguez-Bendala:
“The uniqueness of the Institute is that we have a multidisciplinary team, we are not going to get a cure for type 1 diabetes only from one angle. We need to take care of the autoimmune response, we need to take care of the supply, we need to take care of all the intermediate steps from bench to bedside.
“If I have something that is promising in my lab today, I know that it can be tested right away. So that’s the uniqueness of this institute that makes it very exciting for us to work in.”
Narrator:
This has been a production of the Diabetes Research Institute Foundation.
For more information, or to show your support for the Diabetes Research Institute, call 1-800-321-3437.
You also may donate online at diabetesresearch.org.
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