Israeli Researchers Create Heart Tissue From Patients’ Skin Cells

Breakthrough presents new research opportunities into hereditary heart disease and possible cures.

A catheterization room at Rambam Medical Center in Haifa.
Hagai Frid

Researchers at Rambam Medical Center and the Technion - Israel Institute of Technology have used genetic engineering to turn patients’ skin cells into heart cells, creating entire pieces of heart tissue.

The engineered tissue ends up having the same heart problem that the particular patient had. This opens new possibilities for researching hereditary heart disease and developing targeted, effective drugs to treat heart problems.

The researchers also believe that within a few years anyone who has a heart problem will be able to have his heart significantly reinforced by the injection or implantation of healthy heart cells or tissue developed from the patient’s own body. The solutions presented by the researchers make it possible to speak of “personalized medicine” with regard to heart disease, whereas before the term was associated primarily with cancer treatment.

The research was presented last week at the Rambam Summit, held on the Rambam Health Center Campus. At this stage, the researchers are testing the technology on large animals like pigs.

Right now there are heart cells beating in petri dishes in the lab of Prof. Lior Gepstein, director of Rambam’s cardiology department and a researcher at the Technion. Microscopic close-up photos show how each and every cell alternately shrinks and expands according to the heart rate. This wouldn’t be so unusual except for one thing; only a few weeks ago, these cells were skin cells.

By using a special technique to create what are known as induced pluripotent stem cells, the skin cells were returned to their pre-differentiated stage, before they had developed into specific organs. Using another process, the cells were “nudged” into differentiating themselves into heart cells.

Induced pluripotent stem cells were first generated in 2006 from mouse cells, and a year later scientists managed to create human stem cells in the lab of Shinya Yamanaka at the University of Kyoto in Japan. Gepstein’s lab has been dealing with stem cells for more than 15 years. In 2001, he and his colleagues first succeeded in creating human heart cells from embryonic stem cells. In 2009 they were among the pioneers in creating human heart cells from induced pluripotent stem cells.

Gepstein and his team are using these stem cells in two ways. One is to implant the heart cells made from the stem cells to improve the performance of a failing heart. The other is to use heart cells developed from patients with hereditary diseases to research genetic diseases that affect the heart and to develop remedies for them.

“The idea is that if someone has a heart attack and suffers from heart failure we can implant these cells to the damaged areas,” Gepstein explains. “Our goal is to get to the clinical trial stage within 4-5 years, with the first stage being transplanting cells to the damaged areas, while in later stages we want to engineer tissue and implant entire tissues in these regions.”

At the same time, the researchers found that heart cells developed from skin cells taken from patients with hereditary heart problems that cause arrhythmia, cardiac arrest and death at a young age, could be used to form tissue that precisely express whatever problem that particular patient had. This proves that “the genetic mutation [that causes the heart problem] is present in all the body’s cells,” said Geptstein.

Hereditary arrhythmia is one of the primary causes of sudden death in children and adults under age 35. “The problem was that we couldn’t study the hearts of the patients themselves, and we couldn’t study heart cells, either, because as soon as we took them off the heart, they would die,” Gepstein says. “The new method we are proposing is to take skin cells from these patients, create heart cells from them and study them in the lab. That’s how we will be able to understand these diseases, find the optimum treatment and even try to prevent the disease.”