10 Years of Intracoronary and Intramyocardial Bone Marrow Stem Cell Therapy of the Heart

Abstract

Intracoronary and intramyocardial stem cell therapy aim at the repair of compromised myocardium thereby--as a causal treatment--preventing ventricular remodeling and improving overall performance. Since the first-in-human use of bone marrow stem cells (BMCs) after acute myocardial infarction in 2001, a large number of clinical studies have demonstrated their clinical benefit: BMC therapy can be performed with usual cardiac catheterization techniques in the conscious patient as well as also easily during cardiosurgical interventions. New York Heart Association severity degree of patients as well as physical activity improve in addition to ("on top" of) all other therapeutic regimens. Stem cell therapy also represents an ultimate approach in advanced cardiac failure. For acute myocardial infarction and chronic ischemia, long-term mortality after 1 and 5 years, respectively, is significantly reduced. A few studies also indicate beneficial effects for chronic dilated cardiomyopathy. The clinical use of autologous BMC therapy implies no ethical problems, when unmodified primary cells are used. With the use of primary BMCs, there are no major stem cell-related side effects, especially no cardiac arrhythmias and inflammation. Various mechanisms of the stem cell action in the human heart are discussed, for example, cell transdifferentiation, cell fusion, activation of intrinsic cardiac stem cells, and cytokine-mediated effects. New techniques allow point-of-care cell preparations, for example, within the cardiac intervention or operation theater, thereby providing short preparation time, facilitated logistics of cell transport, and reasonable cost effectiveness of the whole procedure. The 3 main indications are acute infarction, chronic ischemic heart failure, and dilated cardiomyopathy. Future studies are desirable to further elucidate the mechanisms of stem cell action and to extend the current use of intracoronary and/or intramyocardial stem cell therapy by larger and presumably multicenter and randomized trials.

Stem Cell Therapy for Heart Disease

“…19 It is simple and noninvasive, relying on post-AMI physiological signals to target cells towards damaged tissues. 28 Unfortunately, it is inefficient and impractical, as large cell numbers and infusions are necessary for sufficient amounts to reach infarct-related arteries, 29 due to confinement in the microvasculature and losses to other organs. 28,29 Direct intramyocardial injection during coronary artery bypass graft (CABG) surgery easily allows stem cells to be placed into the targeted zone.…”

“…28 Unfortunately, it is inefficient and impractical, as large cell numbers and infusions are necessary for sufficient amounts to reach infarct-related arteries, 29 due to confinement in the microvasculature and losses to other organs. 28,29 Direct intramyocardial injection during coronary artery bypass graft (CABG) surgery easily allows stem cells to be placed into the targeted zone. 29 Suitable candidates include chronic ischemic HF patients, because chronically infarcted tissue does not release the necessary post-AMI physiological signals to attract and mobilize cells to the infarct zone.…”

“…28,29 Direct intramyocardial injection during coronary artery bypass graft (CABG) surgery easily allows stem cells to be placed into the targeted zone. 29 Suitable candidates include chronic ischemic HF patients, because chronically infarcted tissue does not release the necessary post-AMI physiological signals to attract and mobilize cells to the infarct zone. 19,28 However, only a small amount of cells survive more than three days, 30 because the microenvironment is problematic for cell survival secondary to inflammation and insufficient blood supply.…”

“…28 Transendocardial injection is similar to the intramyocardial route, but uses a flexible catheter-based percutaneous technique across the aortic valve. 29 Injecting cells in and around the infarct zone 22 allows greater cell engraftment, 28 while using fewer cells. 22 Potential risks include myocardial perforation, AMI, and induction of ventricular arrhythmias.…”

“…22 Potential risks include myocardial perforation, AMI, and induction of ventricular arrhythmias. 23,28,29 Intracoronary infusion into the infarct-related artery is the most popular in AMI trials. 19 Cells are injected via a catheter into the affected artery.…”