Jerusalem Post

Potential cure for heart disease, diabetes By Judy Siegel

JERUSALEM (August 2) - Heart-attack victims and insulin-dependent diabetics have cause for celebration. Thanks to two separate pieces of major medical research at the Technion-Israel Institute of Technology and Rambam Hospital in Haifa, the replacement of scarred muscle tissue and insulin-producing pancreas cells is an ever-nearing prospect.

The prestigious Journal of Clinical Investigation yesterday published an article by Dr. Itzhak Kehat and Dr. Lior Gepstein of the Technion's Rappaport Faculty of Medicine and Rambam on how they are reportedly the first in the world to grow human heart cells in a lab from embryonic stem cells. These precursor cells can be regarded as the body's first building blocks, having the amazing ability to transform themselves into virtually every cell type. This ability enables the embryo to grow from a round ball made from a handful of cells into a fully formed body.

Meanwhile, the no-less-prestigious journal Diabetes yesterday published a study by Dr. Karl Skorecki of the same medical faculty, who with his team demonstrated that human embryonic stem cells can produce insulin. This important research could signal an important step for a cure of type I (juvenile-onset, insulin-dependent) diabetes.

Both teams worked in cooperation with Prof. Joseph Itskovitz, a medical faculty colleague and director of obstetrics and gynecology at Rambam, who three years ago helped isolate a line of human embryonic stem cells in pioneering work with University of Wisconsin researchers three years ago.

Samples from this same line of stem cells - which, under certain conditions, work like a factory to produce an unending supply of stem cells - were taken from embryos frozen for years but not used for in-vitro fertilization. They were then given to the two Technion teams, which succeeded in producing heart tissue and insulin-producing cells.

After growing an undifferentiated mass of cells by a now-standard technique, Gepstein and his team shifted the cells into a special growth suspension of fibroblasts taken from mice. "No one knows why this works," said Gepstein,

As they divided, the stem cells aggregated into microscopic clumps called embryoid bodies. In about a 10th of the embryoid bodies, the researchers found small groups of cells that were spontaneously contracting, just as do the cells that develop into heart tissue in an embryo.

While other researchers recently reported that they had used stem cells from bone marrow to repair mouse hearts, the Gepstein team's research is a step forward in two important ways: It is the first time, he said, "that human - as opposed to mouse - stem cells have been induced to form proto-heart cells. In addition, it is the first time that human embryonic stem cells have been made to differentiate into heart cell tissue.

"Embryonic stem cells have advantages over stem cells derived from adult tissues. They can proliferate far more than can stem cells from adults, producing far more descendant cells. This is important, because many millions of cells are needed to repair organs.

"We also know that embryonic stem cells can differentiate into all the tissues of the body, while a given type of adult stem cell seems to differentiate into only a small set of tissue types. So the technique could be modified to produce other types of human tissue."

The amazing thing about the approximately 40,000 human heart cells that Gepstein's team produced - to form tissue about one square millimeter in size - is that they contract like a pulsing heart. They are fed by a growth medium, without blood vessels.

"We wanted to be sure they were indeed early-stage cardiomyocytes and thus destined to differentiate into heart cells. We tested for unique cardiac proteins and for electrical activity, as with an electrocardiogram. We administered adrenaline, and the hormone made the cells pump faster as in a heart. We also looked at the cells' structure under an electron microscope and at their chemical activity, such as their uptake of calcium. All this convinced us they were cardiomyocytes."

The major task facing the team is to produce commercial amounts of heart cells for heart repair; this could be done with growth factors and purifying them through the use of markers for heart cells, Gepstein said. But how will these cells make the leap to replacing scarred muscle in patients unable to exert themselves or enjoy a normal life?

Gepstein said that cloning compatible embryos for heart patients remains science fiction. Instead, one might create 20 basic immunological types of cells that would suit almost anyone, using immunosuppressants to prevent rejection if necessary.

"I can't say how long the discovery will take to be applied on patients, but the demand is great, and this field will push ahead rapidly," he said.

When a heart attack occurs, he continued, the section of the heart that doesn't get an adequate supply of blood dies and is replaced by scar tissue that can't regenerate and will no longer be able to pump blood. So this can lead to reduced heart function and eventually to heart failure. The goal would be to inject the early-stage human heart cells created in the laboratory using stem cells into the damaged area and create healthy cardiac muscle that restores heart function.

"Patients with end-stage heart failure are often dependent on the availability of heart donors," said medical faculty dean and Rambam cardiology interventionist Prof. Rafael Beyar. "This new research may lead to breakthrough interventional tools to treat this devastating disease."

Meanwhile, Skorecki's work offers promise for an eventual cure of type I diabetes, which results from the autoimmune destruction of pancreatic islet cells that produce the insulin. The only way to cure the disease is by pancreas transplantation, but the supply of such organs is meager. The new study "offers the promise that stem cells might provide a rich source of insulin-producing cells and put us closer to a cure for this serious disease," said Dr. Christopher Saudek, president of the American Diabetes Association.

-- Anonymous, August 02, 2001