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Unbreak that heart
SAN FRANCISCO—A $10 million, seven-year grant funded by the National Heart, Lung and Blood Institute (NHLBI) has empowered scientists at the Gladstone Institute of Cardiovascular Disease (GICD) and Stanford University School of Medicine to conduct research aimed at discovering how pluripotent stem cells, or iPS cells, can repair damaged heart muscle and develop regenerative medicine therapies for cardiac patients.
The ambitious collaborative effort will be conducted by investigators led by GICD Director Dr. Deepak Srivastava, and a Stanford team led by Dr. Robert Robbins, professor and chair of cardiothoracic surgery.
However, the Gladstone-Stanford research project represents just a fraction of a wide-ranging effort that includes the technology programs of 17 multidisciplinary teams in nine research hubs, coordinated out of the University of Maryland-Baltimore. Each research team will receive approximately $10 million over seven years as part of the NHLBI Progenitor Cell Biology Consortium.
NHLBI Director Dr. Elizabeth Nabel says the NHLBI is committed to stimulating stem cell research leading to regenerative therapies for the treatment of heart, lung and blood diseases.
"Important gaps remain in our understanding of stem and progenitor cells, and this consortium holds great promise to expand our knowledge and uncover therapeutic applications of great public impact," Nabel says.
Stanford cardiac specialist Robbins says, "This consortium brings together the leading scientists in this field in a large-scare coordinated effort that may be a 'Manhattan Project' of stem cell research. The aim is to investigate and evaluate the potential of this for the major diseases of our time."
The partnership between the two prestigious institutions is a good fit, Srivastava said.
"We had natural synergy in bringing Gladstone's expertise in iPS cells and cardiac cell differentiation together with Stanford's expertise in imaging cells in animals, doing preclinical trials on large animal and bioengineering," Srivastava says. "The personalities of the investigators are also synergized, and we realized that together we can accomplish more—and have more fun doing it. We hope to be able to efficiently guide induced pluripotent stem (iPS) cells to become heart cells, fashion them in a way that they can be introduced into damaged hearts, test their efficacy in large animals and prepare for a clinical trial," Srivastava said.
Induced pluripotent stem cells are derived from adult stem cells, like the skin, that are manipulated to achieve embryonic-like qualities, he said. Stem cells from human embryos are pluripotent, meaning they can develop into any cell type.
Molecular and biochemical analyses of normal and mutated human genes, including the study of disease-specific iPS cells, provide insights into the mechanisms underlying normal and abnormal cardiac developmental decisions. This technology was developed by Gladstone investigator Dr. Shinya Yamanaka.
Reprogramming adult cells to function like embryonic stem cells is one way researchers hope to create patient-specific cell lines to regenerate tissue or to study specific diseases in the laboratory, Srivastava says.
Stanford has also found a different, rather unconventional method of inducing pluripotent stem cells.
A study by Stanford researchers published online Sept. 8 in the Proceedings of the National Academy of Science, found it was easier and just as safe to make stem cells from fat cells freshly isolated from patients; for instance, from cells present in liposuction "leftovers," than it was to make them from skin cells as other studies have done recently.
"Thirty to 40 percent of adults in this country are obese," reported cardiologist Dr. Joseph Wu, the paper's senior author. "Not only can we start with a lot of cells, we can reprogram them much more efficiently. Fibroblasts, or skin cells, must be grown in the lab for three weeks or more before they can be reprogrammed. But these stem cells from fat are ready to go right away."
Researchers and medical professionals believe there is compelling evidence for urgency—since heart problems affect children, as well as adults. Heart disease is one of the biggest killers in the civilized world, and as populations age, this trend will increase dramatically, Gladstone researchers stated in a public abstract. Currently, the only way to treat failing hearts is with expensive and relatively ineffective drugs, or by heart transplantation.
"Ideally, we would like to be able to regenerate sick or dead heart tissue," the researchers stated. "The best strategy would be to make new heart cells that match the patients' cells (to avoid rejection), and inject them into diseased heart so that they could regenerate the sick heart. Unfortunately, current strategies that are planned to do so are ineffectual."
If the approach of "reprogramming" stem cells into heart cells is successful, these newly generated stem cells could be used for regenerative therapies in the future, researchers say, thus saving the lives of countless heart attack and heart damaged patients.