Could Heart Tissue Be Replaced?

Scientists at the Medical College of Wisconsin will conduct experiments involving reprogramming of stem cells in pursuit of a new frontier in heart therapy thanks to a five-year, $8 million grant from the National Institutes of Health.

The work will attempt to develop a tool doctors have never before possessed: the ability to replace damaged heart tissue.

Up to now, researchers have been able to grow cardiac myocytes, the cells that cause the heart to beat, from primitive embryonic stem cells and from cells made using a relatively new technique, cell reprogramming. Reprogramming of human cells, pioneered by the labs of James Thomson in Madison and Shinya Yamanaka in Japan, allows scientists to take a person's skin cell and turn it into something very similar to an embryonic stem cell. By giving a cell a fresh start, they can then coax it into becoming a heart cell.

"But there is a challenge in the basic biology" of this approach, said John Lough, head of the Medical College team on this project and a professor of cell biology, neurobiology and anatomy.

Lough said scientists have been unable to make pure populations of these beating heart cells. The best they've been able to do is make populations that are about 50% pure. Impure cell populations would be unsafe for transplant into humans. For example, if those populations contained primitive embryonic-like stem cells, they would have the ability to become many other kinds of tissue, including tumor cells.

Lough and the scientists working with him will try to solve this problem.

For example, another Medical College stem cell scientist on the research team, Stephen Duncan, has identified two transcription factors, proteins that regulate gene activity, that are necessary for the development of these beating heart cells. He will extend this knowledge to develop purer populations of the cardiac myocytes.

Another team member, Stephen Dalton, a professor of biochemistry and molecular biology at the University of Georgia, has created millions of cells having characteristics of an extremely rare cardiac stem cell. He has created the millions of cells using primitive stem cells. Dalton will investigate whether his cells are equivalent to this rare adult stem cell and whether they can repair damaged adult heart muscle.

Lough said the project's aim is to create millions of pure cardiac myocytes by using the signals and mechanisms learned from previous work that explored how the heart forms in the embryo. Investigators will attempt to re-create those processes in a laboratory dish.

In collaboration with Medical College professors John Auchampach and Paula North, team members will use cardiac myocytes generated through their work in experiments with mice and possibly rats. They hope to learn whether the cells they've made can engraft and repair damaged hearts of these lab animals.

At present, work involving embryonic stem cells is on hold until the NIH approves cell lines that meet its new guidelines. However, the work involving cells made through reprogramming will be able to proceed, Lough said.