Cardiovascular disease (CVD) affects 81.1 million Americans, with more women than men impacted. The cost of CVD in the United States for the year 2010 was estimated at $503.2 billion. By comparison, the estimated cost of all cancer was $228 billion (www.americanheart.org). Cardiovascular disease therefore represents a huge negative impact to Americans, through lives lost, quality of life diminished, and massive Healthcare costs.
Regenerative medicine provides hope for patients suffering a heart atack. After an attack there is reduced bloodflow to one wall of the heart, and if uncorrected the entire region can form a dense collagen scar that cannot contract, leading to heart failure. It is known that mesenchymal stem cells from the bone marrow can release factors that can cause tissue remodeling, reducing scarring and fibrosis, if they are in the right place at the right time. However optimal delivery methods have not yet been found for these cells, and that is the basis for our curent application.
Clinical application of cell-based regenerative therapy for patients with heart disease and heart attack has so far relied on the injection of suspensions of cells either intravenously or directly into the heart. The variable results seen in most trials published to date may be due to sub-optimal cell source, timing of delivery, and poor cell retention and survival in the target tissue, as well as the absence of favorable microenvironment in the chronically diseased tissue. The donor cells are usually placed into the heart in liquid single cell suspension, and are injected into a damaged and hostile microenvironment, often where they cannot even attach properly. This strategy has not been optimal for cell survival and does not encourage the cells to provide "paramedic" functions to the surrounding damaged tissue. They often just die, like the surrounding tissue, if injected into a scarred region of other dying cells.
Stem cells need a healthy matrix scaffold or “trellis” to keep them in place in the damaged tissue, and to ensure that they are healthy while they are working to correct tissue damage at the site of injury. Our strategy for the proposed clinical trial is to implant mesenchymal stem cells (MSCs) from a healthy donor’s bone marrow into the heart on a healthy and commercially available (FDA-approved) matrix. From this healthy “trellis” they can survive and release factors that can work to decrease scarring after heart attack and to remodel healthy tissue, and to improve the blood supply into the damaged tissue. The matrix that we are using is safe and has been used in tens of thousands of clinical cardiac repair surgeries. By combining the healthy matrix and the stem cells we hope to achieve benefits that transcend simple synergy.
More than 17 million Americans currently alive have a history of coronary heart disease. In 2006, almost half a million Americans died from coronary heart disease and an estimated 1.26 million will have a new or recurrent coronary event this year. Advances in treatment have decreased early mortality but consequently lead to an increase in the incidences of heart failure. Patients with congestive heart failure have a 50 percent readmission rate within six months, which is a heavy cost both in terms of quality of life and financially. The high cost of caring for patients with congestive heart failure (CHF) results primarily from frequent hospital readmissions for exacerbations. There is a huge need for efficient treatment strategies that address the underlying cause, massive loss of functional myocardium.
Given current optimal standard of care and the emerging results from current late stage clinical trials with cell based regenerative surgery, we propose that a significant improvement in mortality and morbidity relating to congestive heart failure may be achieved by a cell therapy based device that combines two or more of the following requirements: Readily incorporated with current standard of care, non-immunogenic, improve mechanical support, promote localized retention of donor cells, promote survival of the donor cells in and around the target tissue, confer rapid improvement in cardiac function, integrate with the host tissue, promote host tissue endogenous repair and beneficial remodeling. We believe that a MSC seeded extracellular matrix (ECM) “patch” device will meet most of these criteria and as an adjunct therapy will afford a significant improvement in mortality and morbidity in a large group of patients who are at the risk of progressing to end stage heart failure and for whom the improbable prospect of heart transplantation remains the only true curative option.
Heart failure is responsible for >11 million visits to a physician's office and results in 3.5 million hospitalizations per year. One-third of these patients require repeat hospitalization within three months. Heart failure also is the number one hospital expenditure for Medicare. The Benefit to California is in the decrease of costs for the care of this population as well as maintaining or potentially increasing the level of their productivity in the work place and at home, and improving California heart patients’ quality of life.