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Human derived stem cells can repair rat hearts damaged by heart attack
August 27, 2007When human heart muscle cells derived from embryonic stem cells are implanted into a rat after a heart attack, they can help rebuild the animal's heart muscle and improve function of the organ, scientists report in the September issue of Nature Biotechnology. The researchers also developed a new process that greatly improves how stem cells are turned into heart muscle cells and then survive after being implanted in the damaged rat heart. The findings suggest that stem-cell-based treatments might one day help people suffering from heart disease, the leading cause of death in most of the world.
The study was conducted by researchers at the University of Washington School of Medicine in Seattle and at Geron Corp. in Menlo Park, Calif. The scientists set out to tackle two of the main challenges to treating damaged hearts with stem cells: the creation of cardiac cells from embryonic stem cells, and the survival of those cells once they are implanted in a damaged heart.
"Past attempts at treating infarcted hearts with stem cells have shown promise, but they have really been hampered by these challenges," explained Dr. Chuck Murry, director of the Center for Cardiovascular Biology in the UW Institute for Stem Cell and Regenerative Medicine, and corresponding author on the study. "This method we developed goes a long way towards solving both of those problems. We got stem cells to differentiate into mostly cardiac muscle cells, and then got those cardiac cells to survive and thrive in the damaged rat heart."
Embryonic stem cells can differentiate, or turn into, any type of cell found in the body. But researchers had struggled to get stem cells to differentiate into just cardiomyocytes, or heart muscle cells -- most previous efforts resulted in cell preparations in which only a fraction of 1 percent of the differentiated cells were cardiac muscle cells. By treating the stem cells with two growth factors, or growth-encouraging proteins, and then purifying the cells, they were able to turn about 90 percent of stem cells into cardiomyocytes.
The researchers dealt with the other big challenge of stem cell death by implanting the cells along with a cocktail of compounds aimed at helping them grow. The cocktail included a growth "matrix"-- a sort of scaffolding for the cells to latch on to as they grow -- and drugs that block processes related to cell death. When using the pro-growth cocktail, the success rate of heart muscle grafts improved drastically: 100 percent of rat hearts showed successful tissue grafts, compared to only 18 percent in grafts without the cocktail.
"The problem of cell death is pretty common in stem-cell treatments," Murry explained. "When we try to regenerate with liquid tissues, like blood or bone marrow, we're pretty good at it, but we haven't been very successful with solid tissues like skeletal muscle, brain tissue, or heart muscle. This is one of the most successful attempts so far using cells to repair solid tissues -- every one of the treated hearts had a well-developed tissue graft."
When the researchers followed up on the stem-cell treatment by taking images of the rat hearts, they found that the grafts helped thicken the walls that normally stretch out after a heart attack and cause the heart to weaken. The thickened walls were also associated with more vigorous contraction.
"We found that the grafts didn't just survive in the rat hearts -- they also helped improve the function of the damaged heart," said Dr. Michael Laflamme, UW assistant professor of pathology and the lead author of the study. "That's very important, because one of the major problems for people suffering a myocardial infarction is that the heart is damaged and doesn't pump blood nearly as well. This sort of treatment could help the heart rebound from an infarction and retain more of its function afterwards."
The next step in studying stem-cell treatments for the heart is to conduct similar experiments in large animals, like pigs or sheep, while further refining the treatment in rats. Early human clinical trials could begin in about two years, Murry said.
University of Washington
Embryonic stem cells can differentiate, or turn into, any type of cell found in the body. But researchers had struggled to get stem cells to differentiate into just cardiomyocytes, or heart muscle cells -- most previous efforts resulted in cell preparations in which only a fraction of 1 percent of the differentiated cells were cardiac muscle cells. By treating the stem cells with two growth factors, or growth-encouraging proteins, and then purifying the cells, they were able to turn about 90 percent of stem cells into cardiomyocytes.
The researchers dealt with the other big challenge of stem cell death by implanting the cells along with a cocktail of compounds aimed at helping them grow. The cocktail included a growth "matrix"-- a sort of scaffolding for the cells to latch on to as they grow -- and drugs that block processes related to cell death. When using the pro-growth cocktail, the success rate of heart muscle grafts improved drastically: 100 percent of rat hearts showed successful tissue grafts, compared to only 18 percent in grafts without the cocktail.
"The problem of cell death is pretty common in stem-cell treatments," Murry explained. "When we try to regenerate with liquid tissues, like blood or bone marrow, we're pretty good at it, but we haven't been very successful with solid tissues like skeletal muscle, brain tissue, or heart muscle. This is one of the most successful attempts so far using cells to repair solid tissues -- every one of the treated hearts had a well-developed tissue graft."
When the researchers followed up on the stem-cell treatment by taking images of the rat hearts, they found that the grafts helped thicken the walls that normally stretch out after a heart attack and cause the heart to weaken. The thickened walls were also associated with more vigorous contraction.
"We found that the grafts didn't just survive in the rat hearts -- they also helped improve the function of the damaged heart," said Dr. Michael Laflamme, UW assistant professor of pathology and the lead author of the study. "That's very important, because one of the major problems for people suffering a myocardial infarction is that the heart is damaged and doesn't pump blood nearly as well. This sort of treatment could help the heart rebound from an infarction and retain more of its function afterwards."
The next step in studying stem-cell treatments for the heart is to conduct similar experiments in large animals, like pigs or sheep, while further refining the treatment in rats. Early human clinical trials could begin in about two years, Murry said.
University of Washington
Stem Cells Current Events and Stem Cells News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Umbilical cord blood stem cell transplant may help lung, heart disorders
Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
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