A combination of heart cells derived from human stem cells could be the answer to developing a desperately-needed treatment for heart failure, according to new research part-funded by the British Heart Foundation (BHF) and published in Nature Biotechnology.
Researchers have found that, by transplanting an area of damaged tissue with a combination of both heart muscle cells and supportive cells taken from the outer layer of the heart wall, they may be able to help the organs recover from the damage caused by a heart attack.
Scientists have been trying to use stem cells to repair damaged hearts for a number of years.
Efforts have been unsuccessful so far, mainly because the vast majority of transplanted cells die within a few days.
Now, Dr. Sanjay Sinha and his team at the University of Cambridge, in collaboration with researchers at the University of Washington, have used supportive epicardial cells developed from human stem cells to help transplanted heart cells live longer.
The researchers used 3-D human heart tissue grown in the lab from human stem cells to test the cell combination, finding that the supportive epicardial cells helped heart muscle cells to grow and mature.
They also improved the heart muscle cell’s ability to contract and relax.
In rats with damaged hearts, the combination also allowed the transplanted cells to survive and restore lost heart muscle and blood vessel cells.
Researchers now hope to understand how the supportive epicardial cells help to drive heart regeneration.
Understanding these key details will bring them one step closer to testing heart regenerative therapies in clinical trials.
Hundreds of thousands of people in the UK are living with debilitating heart failure, often as a result of a heart attack.
During a heart attack, part of the heart is deprived of oxygen leading to death of heart muscle.
This permanent loss of heart muscle as well as subsequent scarring combines to reduce the heart’s ability to pump blood around the body.
People suffering from heart failure can’t regenerate their damaged hearts and the only cure is a heart transplant.
Ultimately, these researchers hope that, by harnessing the regenerative power of stem cells, they will one day be able to heal human hearts using a patient’s own cells.
Left-hand side shows heart muscle cells alone and no muscle contraction. Right-hand side shows greater muscle contraction and relaxation with the combination of heart muscle cells and additional stem cell-derived supportive epicardial cells. Credit: Dr. Sanjay Sinha, BHF-funded researcher, University of Cambridge, UK
In addition to the BHF, this research was funded by the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR).
Dr. Sanjay Sinha, BHF-funded researcher and leader of the study at the University of Cambridge, said:
“There are hundreds of thousands of people in the UK living with heart failure – many are in a race against time for a life-saving heart transplant.
But with only around 200 heart transplants performed each year in the UK, it’s absolutely essential that we start finding alternative treatments.”
Dr. Johannes Bargehr, first author of the study at the University of Cambridge said:
“Our research shows the huge potential of stem cells for one day becoming the first therapy for heart failure.
Although we still have some way to go, we believe we’re one giant step closer, and that’s incredibly exciting.”
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation which part-funded the research said:
“Despite advances in medical treatments, survival rates for heart failure remain poor and life expectancy is worse than for many cancers.
Breakthroughs are desperately needed to ease the devastation caused by this dreadful condition.
“When it comes to mending broken hearts, stem cells haven’t yet really lived up to their early promise.
We hope that this latest research represents the turning of the tide in the use of these remarkable cells.”
The BHF has invested millions of pounds in research to harness the power of stem cells in treating heart and circulatory diseases.
The charity has funded three Centres of Regenerative Medicine across the UK, housing some of the world’s leading experts.
Cardiovascular diseases that damage the heart and lead to Heart Failure (HF), stimulate myocytes death and generation of fibrosis, as well as ventricular remodeling [1].
Heart failure is considered, deadly, incapacitating and a heavy disorder worldwide. The occurrence of HF in developed countries has extended epidemic proportions increasingly. However, the estimate HF patients referred to the hospital remains low. In the United States, HF is reported to affect about 6 million individuals, with more than 300,000 deaths annually, which costs over 40 billion dollars in the health care service [2].
Recent therapeutic approaches in HF patients increase the lifespan, but so far no document has been reported the essential efforts for the repair of cardiac tissue. Stem cells are cell types distinguished by their ability of self-renewal as well as their capacity to differentiate into developed progenitor cells that themselves could discriminate into specific matured cells types [3,4].
Throughout the past 15 years, various preclinical and clinical studies investigated the capability of numerous stem cells to progress cardiac function and weaken adversative Left Ventricular (LV) remodeling in heart diseases [5].
In spite of this quick development, various essential questions arise which need to be determined, beside the fact that up to now no operative cell therapy in patients with cardiomyopathy has been reported.
Afterward two decades of focused investigation and efforts of clinical trials, stem cell based therapies for cardiac diseases are not receiving nearer to clinical accomplishment [6].
This review addresses the existing state of advancement of Stem Cell (SC) therapy in heart diseases.
We summarize the impact of studies conducted regarding the use of Induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESC), Cardiac Stem Cells (CSC), and Skeletal Myoblasts (Fig.1), and argue current debates, unsolved problems, as well as the prospective instructions.
More information: Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration, Nature Biotechnology (2019). DOI: 10.1038/s41587-019-0197-9 , https://www.nature.com/articles/s41587-019-0197-9
Journal information: Nature Biotechnology
Provided by British Heart Foundation
