Adult stem cells may reduce damage following heart attack

March 29, 2001

New York, NY, March 30, 2001--Researchers from Columbia University College of Physicians & Surgeons have developed an experimental treatment that, in rats, dramatically improves the recovery prospects after heart attack, using stem cells from human adults. The discovery, published in the April 1 issue of Nature Medicine, may lead to new clues for treatments of heart disease, the foremost killer of people in the industrialized world.

The therapy spurs new blood vessel development in heart tissue following a heart attack, preventing the tissue starvation and death that typically causes heart failure.

Dr. Silviu Itescu, M.D., lead author, researcher and faculty member at Columbia University College of Physicians & Surgeons and director of transplantation immunology at Columbia Presbyterian Medical Center of NewYork-Presbyterian Hospital, and colleagues identified a type of stem cell, present in adult human bone marrow, capable of blood vessel development. The researchers injected these cells into rats that had suffered heart attacks two days earlier. The cells went exclusively to the damaged heart tissue, where they triggered the formation of new blood vessels.

This largely fixed a problem that usually follows a heart attack. "The heart muscle itself is able to compensate for the initial loss in heart tissue by increasing in size following a heart attack," Dr. Itescu said. "For every cell lost after the initial heart attack, others enlarge and take over its function, a process termed compensatory hypertrophy. However, the heart can't develop an adequate blood vessel network to nourish these larger cells. Consequently they die, leading to further heart muscle loss, its replacement with fibrous [scar] tissue, and eventually heart failure and death."

The researchers hypothesized, and showed, that the enlarged heart muscle cells require more oxygen. "If you don't supply them with more oxygen and nutrients, they starve to death," Dr. Itescu said.

The new experimental treatment gets to the core of the problem by helping to ensure that the enlarged, but still viable, heart cells are nourished. This keeps them from undergoing apoptosis, a type of cellular "suicide" or programmed cell death, which leads to conversion of heart muscle into non-functional fibrous or scar tissue.

The researchers began by reviewing developmental medical literature on stem cells, which shows that a type of stem cell called an angioblast is largely responsible for developing the fetal vascular system. The researchers identified a similar type of cell, present in tiny amounts in adult human bone marrow. They extracted, purified and multiplied these human cells in the laboratory, then injected them into the tails of rats that had been induced to have heart attacks two days earlier.

The angioblasts found their way to the damaged heart tissue because this tissue produces special signals, called chemotactic ligands, which the angioblasts recognize through receptors on their surfaces. The angioblasts homed to the damaged area and started producing new vessel networks. They also spurred the development of the rat's own vessels in the immediate vicinity, probably by releasing additional chemicals called trophic factors, Dr. Itescu said.

Adults probably already have a system that partially replicates this process of using angioblasts to help repair damaged heart tissue, but it is inadequate, Dr. Itescu explained. The experimental treatment gives the system a concerted boost.

The treatment led to sustained improvements in heart function of between 30 percent and 40 percent in the rats compared with untreated rats. This assessment was based on widely accepted tests of heart function, such as ejection fraction, which measure the efficiency of the pumping action.

These improvements were sustained throughout the four months of the experiment. In addition, the rats treated with the stem cells developed less than one-third the amount of heart scar tissue compared with the untreated animals, Dr. Itescu noted.

The rats didn't reject the human cells and tissue because their own immune systems had been disabled. The use of human cells, rather than rat cells, was a shortcut the researchers took to bring the procedure that much closer to human trials, Dr. Itescu said.

However, there are obstacles to human trials. For instance, it takes several days to culture the cells to quantities large enough to be useful, which ordinarily would make it difficult to treat humans within the same two-day time spans as the rats in this study.

Dr. Itescu said the treatment might still be beneficial if initiated a few days after the heart attack, but the precise window needs to be defined.

One possible approach, Dr. Itescu adds, "is to store the stem cells of high-risk patients in a blood bank for immediate use when required as the patient develops a heart attack."
The study was funded by Department of Surgery Columbia University College of Physicians & Surgeons.

Columbia University Medical Center

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to