Dr. Douglas Melton is a leading biologist in cellular research. His ground-breaking work, which focuses on the the developmental biology of the pancreas, aims to provide diabetics with insulin-producing beta-cells. Dr. Melton is a founding member of the International Society for Stem Cell Research. He has been spearheading a collaboration between the Howard Hughes Medical Institute, Harvard University and the Boston In Vitro Fertilization clinic to develop human embryonic stem lines for research purposes. In addition to serving as the Thomas Dudley Cabot Professor of the Natural Sciences at Harvard University, Dr. Melton works as the co-director of Harvard’s Stem Cell Institute and as a lead investigator of the Howard Hughes Medical Institute.
An embryonic stem cell can not only self-renew like all other stem cells, but its special capacity is to make all different kinds of cells. Indeed, it can make blood, it can make nerve, it can make the whole pancreatic islet, the part of the part of the pancreas that makes the hormone insulin. So if one thinks about the significance of that, that means the discovery in the last couple of decades of stem cells has provided us with a reagent, a tool that can make any tissue in the body. It can make all of the skin, brain and nerve, what’s called the ectoderm of the body, the outside of our body. It can make all of the tissues on the inside, the mesoderm, which includes blood, heart, kidney, muscle and bone. And it can make the gut tube, the endoderm, the lung, the liver, the stomach, the pancreas, the intestine.
So to emphasize this, I want to show you a movie, something we do with students in the lab where we take human embryonic stem cells that are growing in a dish and turn them into beating heart cells. So a petri dish has a colony or clones of these human embryonic stem cells growing. And the arrow shows they are under self-renewing conditions. When those conditions are removed, the cells automatically begin to specialize. Here there’s red, yellow, blue, and purple cells, but the ones I want to show you in the movie are human heart cells.
A striking example of human embryonic stem cells becoming a particular kind of cell is presented with a very simple experiment. Here we have human embryonic stem cells growing in a petri dish as colonies. If we remove the conditions that allow them to self-renew, removing that arrow, they will begin to automatically specialize and you can see here, it’s demonstrated or indicated by red, yellow, blue and purple cells. But I wanted to highlight one particular kind of cell that can form here, which is human heart cells.
The movie shows these cells beating. They’re a little tiny clump of cells beating just like a heart. Here are four different examples of it. It might remind you of Edgar Allen Poe’s story, The Telltale Heart, where he couldn’t stop the heart from beating under the floorboards. Here, once we take these human ES cells, as we call them, in a dish making heart cells, they’ll beat for ever and ever. Now, the trouble here is, we’re not making a heart. I want to emphasize that we are making a tiny little clump of cells. And so biologists have been thinking about, how could we use those beating human heart cells to actually make a real heart.
Well, this picture shows the way we might go about doing that. In this case, we’re taking a rodent, a rat heart, and removing all of the cells, leaving a kind of a ghost. You see here the white ghost on the right, which is a de-cellularized rat heart. So it just has the matrix, the kind of scaffolding for a heart, but there aren’t any beating cells there and it’s dead tissue. We can seed that scaffold with human or mouse embryonic stem cells that have been turned into heart progenitors. And they will go on then to form a beating heart. Here you see this heart pumping away which has heart cells that are made from embryonic stem cells. That’s the sort of the beginning of a field called bioengineering where we’re thinking about how we would make organs and then eventually, of course, transplant them into people.
Directed / Produced by Jonathan Fowler and Elizabeth Rodd