Making Life-Saving Procedures Routine Continued:

Currently, the only sources of stem cells that have been used to successfully transplant these patients and save their lives are from either bone marrow from a donor, or from umbilical cord blood (UCB). In both cases, successful transplantation requires making sure that there is a good match between the patient and the donated cells. Cord blood has been a boon to the transplantation field, however, because cells from UCB are not as picky as bone marrow cells from adults.

As Dr. Kuypers explains, “Cord blood matching requirements are still there but they are a little less critical because UCB cells are so naïve, they don’t differentiate between self and not-self quite so strictly. In this way, cord blood has a major advantage over bone marrow.”

The problem with UCB, which is easily collected from a cut umbilical cord after a baby has been born, has been that there are simply not enough stem cells in a typical unit of cord blood to transplant adults.
“Showing that stem cells were in the placenta was not that earth shattering,” says Dr. Kuypers of the first step of the study. “You could expect them to be there, which is why we did the study. The more important question was, can we harvest them?”

The success of using UCB for stem cell transplantation in pediatric patients lead Dr. Kuypers and his colleagues to wonder about the possibility of looking at the placenta as a potential source of stem cells in large enough quantities to transplant adults, but with similarly naïve cells to reduce the need for as strict a match as required with live donors.

“If we can get stem cells out of cord blood, why couldn’t we get stem cells out of placenta, and if we could, wouldn’t it yield enough for an adult to be transplanted?” says Dr. Kuypers. “Could it be that this placenta actually has a role in making blood cells? And if it does, could it be that there are still stem cells around in term placenta? And if there were, could we get them out?”

Hence the study was born that just won the Society of Experimental Biology and Medicine Best Paper Award for 2009. Consisting of three distinct elements, the publication first proved that term placenta, normally delivered from the woman after the baby is born, and then discarded, does in fact contain stem cells, and in large quantities.

“Showing that stem cells were in the placenta was not that earth shattering,” says Dr. Kuypers of the first step of the study. “You could expect them to be there, which is why we did the study. The more important question was, can we harvest them?”

With UCB, clinicians simply stick a needle into one of the three blood vessels that runs through the umbilical cord and extract the blood with the stem cells in it. With placenta however, the stem cells are not in blood, but in the tissue itself. As a result, Drs. Serikov and Kuypers had to look to a different procedure for a potential answer.

“One of the ways we get stem cells from a living donor is to do what we call mobilization. It’s a process that gets the stem cells to become dislodged from their niches in the bone marrow so that you can catch a handful of them and extract them from the blood of the donor . We thought maybe we could do the same thing, and mobilize the stem cells in the placenta with the same agents normally used to get stem cells out of bone marrow.”

And, as Drs. Serikov and Kuypers showed in the second part of their study, they were right. Using a technique called perfusion to circulate an already FDA-approved mobilization agent used to extract stem cells from bone marrow donors, Drs. Serikov and Kuypers were able to successfully extract the stem cells from the placenta tissue.

The third element of the paper, however, was also critical, as it addressed whether or not using placenta as a stem cell source could be equally as cost-effect as using UCB.

To make the use of placenta as a stem cell source cost effective however, there needs to be a way to store the placenta until the stem cells themselves are actually needed, as it is the extraction itself that represents the majority of the cost. Why spend the money to extract the stem cells until you actually need them?

“You don’t know in most cases whether the placenta you have from a baby born today will be used for a transplant 5 years from now, so if you spend a lot of money to get the stem cells out of the placenta and it’s never used, then it’s money wasted. With UCB, we store hundreds of thousands of cord blood units, while we only use a fraction of them for stem cell transplantation,” explains Dr. Kuypers.

“This lead us to wonder if we couldn’t develop a way to store the placenta whole, just as you do with cord blood, and only worry about extracting the cells when we needed it.”
The microscopic picture of placenta, stained for blood cells and blood cell precursors. The nuclei of the cells are stained blue, red cells are red, the other colors identify certain types of cells.
Drs. Serikov and Kuypers were equally successful with this third and last part of the study. Using a novel technique they themselves developed, Drs. Serikov and Kuypers were able to perfuse the placenta with an anti-freeze such that the whole placenta could be stored in liquid nitrogen. A combination that, in Dr. Kuypers’ words, freezes the placenta solid, but still allows for viable stem cell harvesting at a later date.

“This is the key. It means that, similar to cord blood, you can easily store placenta in a freezer for a couple hundred dollars and only extract your cells from it when you actually need them,” says Dr. Kuypers.

The results made the publication a home-run, not just in terms of the latest accolades it is receiving from the Society of Experimental Biology and Medicine, but also in the promise it offers to the thousands of patients in the U.S. alone with life-threatening blood disorders who die every year because they can’t find a proper stem cell donor match.

“Our goal is to make placenta collection a routine enough kind of procedure that anyone who delivers a baby can collect the placenta and have a place to send it immediately for proper storage, making the chances of finding a donor match for the thousands of patients who need transplants that much greater.”

While the academic proof of principle established in the publication is only the first step in getting a new treatment into the clinic, Drs. Serikov and Kuypers are already pursuing the next series of development required to make this a routine procedure both easily adapted in child birth settings and accepted in bone marrow transplant protocols. In particular, Drs. Serikov and Kuypers are actively pursuing grant funding and industry partnerships to take the ground-breaking results to the next level.

“Significant efforts are still needed to move forward,” says Dr. Kuypers, “but the rewards are equally important and a robust protocol that can easily find its way into the clinic on an every day basis has the potential to benefit thousands of patients in the future.”

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