Background: A 73-year-old man with a history of myocardial infarction and hypertension for 5 years suffered heart failure (NYHA III-IV). Methods: 2D echo indicated hypokinesia at septal, left ventricular anterior wall and apical regions. Coronary angiograms demonstrated 60% stenosis in distal left main and 99% stenosis in proximal and distal left anterior descending coronary arteries (LAD). Both proximal artery and middle left circumflex coronary artery (LC) had 90% stenosis, and diffuse stenosis of right coronary artery (RC) was found. Myocardial perfusion imaging using 99mTc-MIBI indicated defective perfusion of left ventricular apex, anterior wall and septal region and severe reduced perfusion of posterior inferior wall. Myocardial metabolic activities (18F-deoxyglucose) also showed comparable reductions. After exposing the heart, LAD, LC, and RC were all completely occluded and bypass procedure could not be completed. Autologous satellite cells were implanted without any complication and the patient had an uneventful recovery. Results: During the first 2 months, he remained in heart failure, and by the third month, he gradually improved and reached NYHA II. At fifth month after the procedure, significant increased ejection fraction (37.1-48.6%) and wall movement with modest reduction of left ventricular systolic diameter (48-45 mm) were observed. Imaging with 18F-deoxyglucose showed dramatic improvement in myocardial metabolic activity with similar improvement in myocardial perfusion (99mTc-MIBI). Conclusion: This is the first successful case of cellular cardiomyoplasty without any conjunctional procedure for patient with severe coronary heart disease and heart failure.

Background: Cellular cardiomyoplasty is the method of transplanting myogenic cells into injured myocardium to restore the lost heart muscle cells and to improve ventricular function. Method: Three patients, all with a history of coronary heart disease, underwent coronary artery bypass grafting and implantation of autologous satellite cells. A muscle biopsy of 2-4 g from the right vastus lateralis muscle was obtained for satellite cell (myogenic stem cell from skeletal muscle) isolation and proliferation before implanted into the donor's heart. The cells were suspended in serum-free medium and injected into 30-40 sites at and around the ischemic areas just before reversing the hypothermic cardioplegia to eliminate arrhythmia and to improve retention. After recovery, each patient was maintained at the intensive care unit for 3-4 days with ECG monitoring before transferring to the patient floor. Results: All patients survived the procedure with an uneventful recovery and were discharged from the hospital. At 3-4 months follow-up examination, increased left ventricular ejection fraction of 11% (35-46%), 5.4% (40-45.4%) and 1% (40-41%) and decreased left ventricular diastolic diameter of 4, 2 and 9 mm were observed for the patients, respectively. Arrhythmia was not detected during the follow-up evaluation by ECG. Improved perfusion (99mTC-MIBI) and increased metabolic activity (18F-deoxyglucose) were found at the sites of satellite cell implantation. Significant increase of wall thickness and movement at the areas of cell injection was also observed using 2D-echo. Conclusion: Cellular cardiomyoplasty using autologous satellite cells is a safe procedure with encouraging beneficial outcomes in patients.

In this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 10^9 Gd(III) ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a non-apoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful ‘theranostic’ agent that provides a novel platform to simultaneously monitor and improve the therapeutic nature of stem cells for the treatment of CVD. It is expected that this new nanotechnology will further catalyze the development of cellular cardiomyoplasty and other stem cell-based therapies for the prevention, detection, and treatment of human diseases.

Cellular cardiomyoplasty is a cell therapy using stem cells or progenitor cells for myocardial regeneration to improve cardiac function and mitigate heart failure. Since we first published cellular cardiomyoplasty in 1989, this procedure became the innovative method to treat damaged myocardium other than heart transplantation. A significant improvement in cardiac function, metabolism, and perfusion is generally observed in experimental and clinical studies, but the improvement is mild and incomplete. Although safety, feasibility, and efficacy have been well documented for the procedure, the beneficial mechanisms remain unclear and optimization of the procedure requires further study. This chapter briefly reviews the stem cells used for cellular cardiomyoplasty and their clinical outcomes with possible improvements in future studies.

Cellular cardiomyoplasty is a cell therapy using stem cells or progenitor cells for myocardial regeneration to improve cardiac function and mitigate heart failure. Since we first published cellular cardiomyoplasty in 1989, this procedure became the innovative method to treat damaged myocardium other than heart transplantation. A significant improvement in cardiac function, metabolism, and perfusion is generally observed in experimental and clinical studies, but the improvement is mild and incomplete. Although safety, feasibility, and efficacy have been well documented for the procedure, the beneficial mechanisms remain unclear and optimization of the procedure requires further study. This chapter briefly reviews the stem cells used for cellular cardiomyoplasty and their clinical outcomes with possible improvements in future studies.