Human Pluripotent Stem Cell-derived Cardiomyocyte Transplantation: Engraftment and survival of cardiac myocytes in medically treated recipients
FDA-approved medications for heart failure patients after myocardial infarction consist of a multi-drug regimen. Patients with heart failure take these medications widely.
The clinical efficacies of each of these medications were tested in clinical trials that did not involve stem cell therapies. Due to the multiplicity of medicines, the choice of medicines for these multi-drug regimens is driven by cost considerations, patient/physician preference and/or tolerability issues.
Pre-clinical and epidemiological studies have demonstrated that some of this medicines have anti-growth and anti-inflammatory effects critical for cardiac recovery while others do not. More recently, some heart failure medications have been implicated in cancer suppression or progression. These processes are critical to the biology of stem cell transplantation and their use may be important in determining the benefit patients may gain from cell-based therapies. However, studies have not yet addressed the effects of heart failure medicines on stem cell biology. In this pre-clinical study, we propose that certain heart failure drugs may be beneficial for engraftment of transplanted stem cells and limit tumor production-a major limitation of translating stem cell therapies to the clinic.
In 2009, 259 Californians died per 100,000 due to heart disease. This translates into ~100,000 Californians dying per year despite access to standard of care therapies. This number of deaths from heart disease is greater than all cancer deaths in the same year. In addition, a 65-year-old patient who suffers a heart attack today has a 20% risk of subsequent hear failure and a 50% risk of death within 5 years. Disease progression occurs despite the use of current FDA-approved medical therapies and is attributable to a lack of heart regeneration along with continued cell loss. Cell-based therapies are being developed as a therapeutic approach that may substantially augment the current standard-of-care therapies. Such regenerative strategies are intended to restore lost myocardium in order to halt further clinical deterioration and improve depressed function. In this pre-clinical study, we propose that certain heart failure drugs may be beneficial for engraftment of transplanted stem cells and limit tumor production-a major limitation of translating stem cell therapies to the clinic. If already FDA-approved drugs that are available in generic forms are helpful to stem cell engraftment, Californians will not have to pay the cost of developing NEW drugs which will drive the cost of health care up. Instead, we propose using already available drugs first if they prove to help stem cell engraftment without toxicity.