Stem Cell Therapy for Heart Failure
Congestive heart failure (CHF) is a complex condition that results from myocardial dysfunction that permits the heart’s ability to circulate blood at the rate necessary to meet the metabolic needs of peripheral tissues and the numerous organs. Now called heart failure (HF), this condition affects around 400,000 new patients each year, and around 200,000 people die in America from the disease every year. There is currently no cure for heart failure, but stem cell therapy shows great promise.
Scientists are developing ways of using the body’s heart matrix to guide maturation of heart cells and prolong the survival of the heart cells. The heart matrix is a rich, intricate scaffold of the heart, serving as a permanent home for the heart cells. It works like sheet music for the heart orchestra, telling the heart cells where to sit and how to function. Researchers home to rebuild the environments that allows immature heart cells to mature, and possible construct adult heart tissue in laboratory settings. This research approach could allow for a realistic approach to transplanting patient-specific heart cells into their damaged organs.
Reversing left ventricular remodeling would involve the enhancement of regeneration of cardiac myocytes, along with stimulation of neovascularization within the affected portion of the myocardium. The aim of stem cell transplantation in heart failure is to restore contractility and blood supply. This is achieved when progenitor cells that can differentiate into cardiac myocytes, or that promote and encourage neovascularization.
Many clinical studies show that bone marrow-derived stem cells contribute to neoangiogenesis during wound healing, ischemia, post-myocardial infarction, endothelialization of vascular grafts, and atherosclerosis. Human studies are showing promise too. Stem cells were delivered by venous and arterial catheters into coronary vessels to supply the ischemic and infarcted tissues.
How do Stem Cells work for Heart Failure?
Two theories emerged regarding how stem cells regenerate cardiomyocytes (heart muscle cells). The first theory holds that a stem cell can give rise to several cardiomyocytes. The second theory holds that mature cardiomyocytes re-enter the mitotic cell cycle to give rise to new cardiomyocytes. Data to support these theories centers around mutative adult progenitor cells in the myocardium that were identified by multiple markers, including c-kit and side population cells. Other data shows that the dominant mechanism involves pre-existing cardiomyocytes.
The proposed theories are thought to work when mature cardiomyocytes undergo partial dedifferentiation and re-enter the cell cycle. Non-cardiomyocytes release paracrine factors that promote the proliferation of existing cardiomyocytes. These cells activate, proliferate, and undergo differentiation into new heart muscle cells. Both embryonic stem cells and pluripotent stem cells can be used to create new heart cells.
Induced pluripotent stem cells are manipulated back into the stem cell state. Heart cells made from stem cells resemble an infant’s heart cells, and they mature after being transplanted to regenerated tissue, making it new again. The scientific community has already had positive results in many clinical studies, and the researchers believe that stem cell therapy is a viable option for heart failure treatment.
Stem Cell Clinical Studies
A meta-analysis of 33 randomized controlled studies involving adult bone marrow stem cell transplantations. The cells were shown to improve cardiac function after myocardial infarction, and all patients had a significant improvement in left ventricular ejection fraction. One well-done randomized and blinded study involved autologous bone marrow cells. Two years after transplantation, participants had improved ventricular function. A large European study confirmed that stem cell therapy for cardiac illness showed safety as well as efficacy.
Around 109 patients were in a study to receive either stem cell therapy or a placebo. The study involved extracting stem cells from the patient’s own bone marrow, and the participants all had heart failure. In the study, stem cell therapy improved the patients’ quality of life and was associated with beneficial results. The outcome measures were walking endurance test and measurement of amount of blood pumped from the left ventricle with each contraction.
In numerous studies, researchers noted improved blood flow and increased left ventricular contractility, suggesting that stem cells offer therapeutic short-term benefit. This data suggests that mobilized peripheral blood progenitor cells play a factor in the revascularization of ischemic myocardium. In an Argentina study, patients with ischemic heart failure were given stem cell therapy along with coronary surgery. The patients who received stem cells had an improved ejection fraction compared to the group who received surgery only. This was evident at 1, 3, and 6 months after treatment.
Researchers induced heart damage in macaque monkeys to study stem cell therapy. Each animal received around 750 million human embryonic stem cell cardiomyocytes, and they were compared to a control group injected with a placebo solution. The researchers found that the ejection fraction of the untreated animals remained unchanged, but those treated with stem cells had more than 50% improvement in their ejection fractions. This treatment rate rose to 66% after three months (average).
Liu YW, Chen B, Yang X, et al. (2018) Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nature Biotechnology, 2018; DOI: 10.1038/nbt.4162
Patel AN, Henry TD, Quyyumi A, et al. (2016) Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. The Lancet, 2016
Patel AN, Feffner L, Vina RF, et al. (2004). Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: A prospective randomized study. Journal Thorac and Cardiovas Surg, 130(6), 1631-1638.