Tuesday, October 22, 2013

How best to deliver stem cells to the heart?

Our grantee Joe Wu of Stanford University just published a paper that goes a long way toward explaining just how laborious it is to develop therapies based on stem cells.

It all sounds so easy. Find a stem cell in the body (or mature certain kind of cell from embryonic or iPS cells), then put that cell in a part of the body that needs it, like in an ailing heart or damaged liver. Done.

Except that it's not quite so easy. Exactly which cell do you want to use? For every "stem cell" there are variations of "almost stem cell" or "stem cell that's just starting to become the cell type you want" that might actually work better. How do you know which to use? You have to spend years isolating those cells and injecting them into animals that mimic the disease to see which work better.

Because before anyone starts injecting cells into people, scientists want to be sure they've got the right cell.

Then there's figuring out how to get the cells into the damaged tissue (this is where Wu's work comes in). Great, you think you have the right cell. But the body is a big, squishy bog with the circulatory system running like a stream throughout, sweeping cells away. Scientists have to plant the cells where they belong if the cells have any hope of helping out.

In Wu's current work, published September 10 in Circulation, he was injecting stem cells from the bone marrow into the hearts of people with a form of heart disease called dilated cardiomyopathy. Some people had the cells injected into the artery leading into the heart, essentially sweeping those cells into the surrounding heart tissue. Other people had the cells injected directly into the heart muscle.

The next day, Wu and his colleagues found more of those bone marrow stem cells in the heart of the people who had the cells injected directly into the muscle.

Six months later, those same people had an easier time walking for six minutes in a lab test and the heart was pumping more effectively. He didn't follow the people longer to know whether the benefits lasted.

In addition to this work, Wu is part of a CIRM disease team trying to develop a therapy for heart failure based on embryonic stem cells. That work goes back to the issue of which cell type is best. The bone marrow stem cells helped the patients somewhat, but the question remains whether there's another cell type that could help even more. The only way to find out is to test the cells and see what happens. Yet another project of Wu's involves seeing if cells placed in the heart on an lab-made substrate might help them work even more effectively than simply placing them in the heart.

Amy Adams

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