Ordinary Heart Cells Become 'Biological Pacemakers' With Injection of Single Gene

Source: Cedars-Sinai Medical Center

Date: December 16, 2012

Summary:

LOS ANGELES – Cedars-Sinai Heart Institute researchers have reprogrammed ordinary heart cells to become exact replicas of highly specialized pacemaker cells by injecting a single gene (Tbx18) – a major step forward in the decade-long search for a biological therapy to correct erratic and failing heartbeats.  The advance will be published in the Jan 8 issue of Nature Biotechnology and also will be available today on the journal’s website.

Cedars-Sinai researchers, employing a virus engineered to carry a single gene (Tbx18) that plays a key role in embryonic pacemaker cell development, directly reprogrammed heart muscle cells (cardiomyocytes) to specialized pacemaker cells. The new cells took on the distinctive features and function of native pacemaker cells, both in lab cell reprogramming and in guinea pig studies.

If subsequent research confirms and supports findings of the pacemaker cell studies, the researchers said they believe therapy might be administered by injecting Tbx18 into a patient’s heart or by creating pacemaker cells in the laboratory and transplanting them into the heart. But additional studies of safety and effectiveness must be conducted before human clinical trials could begin.

Heart muscle cell grafts suppress arrhythmias after heart attacks in animal study Transplanted heart cells

Source: University of Washington
Date: August 5, 2012

Summary:

Researchers have made a major advance in efforts to regenerate damaged hearts. They discovered that transplanted heart muscle cells, grown from stem cells, electrically couple and beat in sync with the heart’s own muscle. The grafts also reduced the incidence of arrhythmias (irregular heart rhythms) in a guinea pig model of myocardial infarction (commonly known as a heart attack). This finding from University of Washington-led research is reported in the Aug. 5 issue of Nature.

Embryonic Blood Vessels That Make Blood Stem Cells Can Also Make Beating Heart Muscles

Source: University of California - Los Angeles Health Sciences
Date: August 2, 2012

Summary:

UCLA stem cell researchers have found for the first time a surprising and unexpected plasticity in the embryonic endothelium, the place where blood stem cells are made in early development. Scientists found that the lack of one transcription factor, a type of gene that controls cell fate by regulating other genes, allows the precursors that normally generate blood stem and progenitor cells in blood forming tissues to become something very unexpected -- beating cardiomyocytes, or heart muscle cells.

The finding is important because it suggests that the endothelium can serve as a source of heart muscle cells. The finding may provide new understanding of how to make cardiac stem cells for use in regenerative medicine. The two-year study is published Aug. 3, 2012 in the peer-reviewed journal Cell.

Mending a Broken Heart -- With a Molecule That Turns Stem Cells Into Heart Cells

Source: Sanford-Burnham Medical Research Institute
Date: August 2, 2012

Summary:

Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham), the Human BioMolecular Research Institute, and ChemRegen, Inc. have been searching for molecules that convert stem cells to heart cells for about eight years -- and now they've found one. Writing in the August 3 issue of Cell Stem Cell, the team describes how they sifted through a large collection of drug-like chemicals and uncovered ITD-1, a molecule that can be used to generate unlimited numbers of new heart cells from stem cells.

Discovery of ‘Master Molecule’ Could Improve Stem Cell Treatment for Heart Attacks

Source: Johns Hopkins University
Date: June 20, 2012

Summary:

Johns Hopkins researchers have discovered that a single protein molecule may hold the key to turning cardiac stem cells into blood vessels or muscle tissue, a finding that may lead to better ways to treat heart attack patients.

Human heart tissue does not heal well after a heart attack, instead forming debilitating scars. However, for reasons not completely understood, stem cells can assist in this repair process by turning into the cells that make up healthy heart tissue, including heart muscle and blood vessels. Recently, doctors elsewhere have reported promising early results in the use of cardiac stem cells to curb the formation of unhealthy scar tissue after a heart attack. But the discovery of a “master molecule” that guides the destiny of these stem cells could result in even more effective treatments for heart patients, the Johns Hopkins researchers say.

In a study published in the June 5 online edition of journal Science Signaling, the team reported that tinkering with a protein molecule called p190RhoGAP shaped the development of cardiac stem cells, prodding them to become the building blocks for either blood vessels or heart muscle. The team members said that by altering levels of this protein, they were able to affect the future of these stem cells.

New Method Generates Cardiac Muscle Patches from Stem Cells

Source: University of Michigan Health System
Date: June 19, 2012

Summary:

A cutting-edge method developed at the University of Michigan Center for Arrhythmia Research successfully uses stem cells to create heart cells capable of mimicking the heart's crucial squeezing action. The cells displayed activity similar to most people's resting heart rate. At 60 beats per minute, the rhythmic electrical impulse transmission of the engineered cells in the U-M study is 10 times faster than in most other reported stem cell studies.

An image of the electrically stimulated cardiac cells is displayed on the cover of the current issue of Circulation Research, a publication of the American Heart Association. For those suffering from common, but deadly heart diseases, stem cell biology represents a new medical frontier. The U-M team of researchers is using stem cells in hopes of helping the 2.5 million people with an arrhythmia, an irregularity in the heart's electrical impulses that can impair the heart's ability to pump blood.

Their objective included developing a bioengineering approach, using stem cells generated from skin biopsies, which can be used to create large numbers of cardiac muscle cells that can transmit uniform electrical impulses and function as a unit. Furthermore, the team designed a fluorescent imaging platform using light emitting diode (LED) illumination to measure the electrical activity of the cells.

The Real Culprit Behind Hardened Arteries? Stem Cells, Says Landmark Study

Source: University of California - Berkeley
Date: June 6, 2012

Summary:

BERKELEY — One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit. The UC Berkeley researchers say that these newly discovered stem cells contribute to artery-hardening vascular diseases that can lead to heart attacks and strokes.

The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.

Instead, a previously unknown type of stem cell — a multipotent vascular stem cell — is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing June 6 in the journal Nature Communications.

New Stem Cell Technique Promises Abundance of Key Heart Cells

Source: University of Wisconsin-Madison
Date: May 28, 2012

Summary:

A team of scientists at the University of Wisconsin-Madison describes a way to transform human stem cells -- both embryonic and induced pluripotent stem cells -- into the critical heart muscle cells by simple manipulation of one key developmental pathway. The technique promises a uniform, inexpensive and far more efficient alternative to the complex bath of serum or growth factors now used to nudge blank slate stem cells to become specialized heart cells. in the Proceedings of the National Academy of Sciences.

The capacity to make the heart cells using induced pluripotent stem cells, which can come from adult patients with diseased hearts, means scientists will be able to more readily model those diseases in the laboratory. Such cells contain the genetic profile of the patient, and so can be used to recreate the disease in the lab dish for study. Cardiomyocytes are difficult or impossible to obtain directly from the hearts of patients and, when obtained, survive only briefly in the lab. Scientists also have high hopes that one day healthy lab-grown heart cells can be used to replace the cardiomyocytes that die as a result of heart disease, the leading cause of death in the United States.

Patients' Skin Cells Turned Into Heart Muscle Cells to Repair Their Damaged Hearts

Source: European Society of Cardiology
Date: 23 May 2012

Summary:

For the first time scientists have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells that are capable of integrating with existing heart tissue. The research, which is published online Wednesday in the European Heart Journal [1], opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived from the patients themselves, this could avoid the problem of the patients’ immune systems rejecting the cells as “foreign”. However, the researchers warn that there are a number of obstacles to overcome before it would be possible to use hiPSCs in humans in this way, and it could take at least five to ten years before clinical trials could start.

The researchers took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes or “transcription factors” (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the cell nucleus. Crucially, this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene.

The researchers also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterwards so as to avoid insertional oncogenesis. The resulting hiPSCs were able to differentiate to become heart muscle cells (cardiomyocytes) just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for this study. Then the researchers were able to make the cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. Within 24-48 hours the tissues were beating together.

Scientists show that lab-made heart cells can be ideal model for disease research, drug testing

Source: Stanford University School of Medicine
Date: April 18, 2012

Summary:

Heart-like cells made in the laboratory from the skin of patients with a common cardiac condition contract less strongly than similarly created cells from unaffected family members, according to researchers at the Stanford University School of Medicine. The cells also exhibit abnormal structure and respond only dully to the wave of calcium signals that initiate each heartbeat.

The finding used induced pluripotent stem, or iPS, cell technology to create heart-muscle-like cells from the skin of patients with dilated cardiomyopathy, which is one of the leading causes of heart failure and heart transplantation in the United States. It adds to a growing body of evidence indicating that iPS cells can faithfully reflect the disease status of the patients from whom they are derived. Using the newly created diseased and normal cells, the researchers were able to directly observe for the first time the effect of a common beta blocker drug, as well as validate the potential usefulness of a gene therapy approach currently in clinical trials.

The research is published April 18 in Science Translational Medicine.

Stem Cells from Pelvic Bone May Preserve Heart Function

Source: Orlando Health
Date: April 11, 2012

Summary:

Stem cells from the pelvic bone may help hearts beat stronger. Doctors and other clinicians at the Orlando Health Heart Institute are researching the use of stem cells from pelvic bone marrow to restore tissue and improve heart function after muscle damage from heart attacks.

Bone Marrow Stem Cells Can Improve Heart Function, Study Suggests

Source: Mayo Clinic
Date: March 24, 2012

Summary:

CHICAGO — A research network led by a Mayo Clinic physician found that stem cells derived from heart failure patients' own bone marrow and injected into their hearts improved the function of the left ventricle, the heart's pumping chamber. Researchers also found that certain types of the stem cells were associated with the largest improvement and warrant further study. The results were presented today at the 2012 American College of Cardiology Meeting in Chicago. They will also be published online in the Journal of the American Medical Association.

Stem Cell Study in Mice Offers Hope for Treating Heart Attack Patients

Source: University of California - San Francisco
Date: February 15, 2012

Summary:

A UCSF stem cell study conducted in mice suggests a novel strategy for treating damaged cardiac tissue in patients following a heart attack. The approach potentially could improve cardiac function, minimize scar size, lead to the development of new blood vessels -- and avoid the risk of tissue rejection. In the investigation, reported online in the journal PLoS ONE, the researchers isolated and characterized a novel type of cardiac stem cell from the heart tissue of middle-aged mice following a heart attack. Then, in one experiment, they placed the cells in the culture dish and showed they had the ability to differentiate into cardiomyocytes, or "beating heart cells," as well as endothelial cells and smooth muscle cells, all of which make up the heart. In another, they made copies, or "clones," of the cells and engrafted them in the tissue of other mice of the same genetic background who also had experienced heart attacks. The cells induced angiogenesis, or blood vessel growth, or differentiated, or specialized, into endothelial and smooth muscle cells, improving cardiac function.

Scientists perform Ontario's first cardiac stem cell transplant

Source: University of Toronto
Date: January 27, 2012

Summary:

University of Toronto faculty members performed the first cardiac stem cell transplant in Ontario recently, using stem cells derived from the patient's own bone marrow, isolated completely within the operating room, and implanted into the heart at the time of coronary bypass surgery. The stem cells were injected following coronary artery bypass graft (CABG) surgery, by a multi-disciplinary team led by Dr. Terrence Yau, a U of T professor of surgery and director of the Cardiac Stem Cell Therapy Program at the hospital’s Peter Munk Cardiac Centre, part of the University Health Network (UHN).

The Toronto Star published a news story on the trial yesterday.

Stem Cell Study Helps Clarify the Best Time for Therapy to Aid Heart Attack Survivors

Source: Mayo Clinic
Date: November 14, 2011

Summary:


ORLANDO, Fla. — A research network led by a Mayo Clinic physician found that stem cells obtained from bone marrow delivered two to three weeks after a person has a heart attack did not improve heart function. This is the first study to systematically examine the timing and method of stem cell delivery and provides vital information for the field of cell therapy. The results were presented this morning at the 2011 Scientific Sessions of the American Heart Association Meeting in Orlando, Fla. They also will be published online in JAMA to coincide with the presentation.

Results of trial using adult stem cells for heart failure triple researchers’ projections

Source: Brigham and Women's Hospital
Date: November 14, 2011

Summary:

ORLANDO, Fla. – Patients suffering from heart failure due to a previous myocardial infarction showed an average of 12 percent improvement one year following an investigative treatment that involved infusing them with their own stem cells. The results triple the 4 percent improvement average the researchers projected for the Phase I trial.

Results of the trial are published today (Nov. 14) in The Lancet and concurrently presented at the American Heart Association Scientific Sessions in Orlando, Fla. They are the first report of administering subjects’ own cardiac stem cells in humans; previous studies have used stem cells harvested from bone marrow.

Phase I trial shows adult stem cell heart treatment three times more effective than expected

Source: University of Louisville
Posted: November 14, 2011 09:03 AM

Summary:

Patients who suffered from heart failure due to a heart attack showed an average of 12 percent improvement in heart function one year after they underwent an investigative treatment that involved infusing them with their own stem cells. Pre-trial projections were for a 4 percent improvement average. University of Louisville researcher Roberto Bolli, the lead investigator on the Phase I clinical trial, will present the findings today at the American Heart Association Scientific Sessions in Orlando, Fla. He also is lead author on a paper set for publication today in The Lancet.

Stem Cells from Cord Blood Could Help Repair Damaged Heart Muscle

Source: University of Bristol
Date: 13 October 2011

Summary:

New research has found that stem cells derived from human cord blood could be an effective alternative in repairing heart attacks. At least 20 million people survive heart attacks and strokes every year, according to World Health Organisation estimates, but many have poor life expectancy and require continual costly clinical care. The use of patient's own stem cells may repair heart attacks, although their benefit may be limited due to scarce availability and aging. The researchers have found heart muscle-like cells grown using stem cells from human umbilical cord blood could help repair heart muscle cells damaged by a heart attack.

The study, led by Professor Raimondo Ascione, Chair of Cardiac Surgery & Translational Research in the School of Clinical Sciences at the University of Bristol, is published online in Stem Cell Reviews & Reports. The study, funded by the British Heart Foundation (BHF) and the National Institute for Health Research (NIHR), found that it is possible to expand up to seven-fold, in vitro, rare stem cells (called CD133+) from human cord blood and then grow them into cardiac muscle cells.

The findings could have major implications on future treatment following a heart attack given that cells obtained from adults following a heart attack may be less functional due to aging and risk factors.

Scientists Offer New Insight into the Regulation of Stem Cells and Cancer Cells

Source: Gladstone Institutes
Date: August 14, 2011

Summary:

Scientists at the Gladstone Institutes have gained new insight into the delicate relationship between two proteins that, when out of balance, can prevent the normal development of stem cells in the heart and may also be important in some types of cancer.
The news, being announced in a paper published online today in Nature Cell Biology, adds to the understanding of the role of stem cells in embryonic heart development, and how that process could be manipulated to create new heart muscle in the future. This paper also provides another example of how the same signals controlling stem cells in the embryo are those that can cause human cancers, providing new insight into treating this devastating disease.

Protein Switch Controls How Stem Cells Turn Into New Heart Tissue

Source: University of Oxford
Date: 12 July 2011

Summary:

Oxford University researchers have identified a protein that can direct stem cells to become either new heart muscle or blood vessels. The research, which was carried out in zebrafish, offers insight into how it might be possible one day to generate tissues to repair the human heart after damage inflicted by a heart attack.

The scientists, based at the MRC Molecular Haematology Unit at the University of Oxford, identified a protein called 'fibroblast growth factor' (Fgf) as the controlling factor which determines whether developing heart cells become heart muscle or blood vessels. They showed that manipulating levels of Fgf in zebrafish embryos could determine how much of each cell type was made.
The research, funded by the Medical Research Council and British Heart Foundation, is published in the journal Development.