June 2, 2005 (received for review April 13, 2005) | Luciano C. Amado*,†, Anastasios P. Saliaris**, Karl H. Schuleri*, Marcus St. John*, Jin-Sheng Xie*, Stephen Cattaneo†, Daniel J. Durand*,†, Torin Fitton†, Jin Qiang Kuang§†, Garrick Stewart*, Stephanie Lehrke*†, William W. Baumgartner†, Bradley J. Martin§†, Alan W. Heldman*†, and Joshua M. Hare*†
This study investigates the use of allogeneic mesenchymal stem cells (MSCs) for cardiac repair after myocardial infarction (MI) in pigs. The researchers conducted a randomized, investigator-blinded, placebo-controlled trial to evaluate the safety and efficacy of intramyocardial injection of MSCs. Key findings include:
1. **Safety and Delivery**: MSCs were safely injected into the damaged myocardium using a percutaneous-injection catheter 3 days after MI, with no adverse events observed.
2. **Engraftment and Cardiac Function**: MSCs resulted in long-term engraftment, reduced scar formation, and near-normalization of cardiac function. MRI imaging and histological analysis confirmed the presence and integration of MSCs into the myocardium.
3. **Allogeneic MSCs**: The transplanted MSCs were prepared from an allogeneic donor and were not rejected, offering a practical advance for widespread application.
4. **Mechanisms of Benefit**: MSCs expressed muscle-specific proteins, suggesting their differentiation into cardiomyocytes. They also stimulated endogenous cellular replication, contributing to cardiac regeneration.
5. **Impact on Infarct Size**: MSC treatment significantly reduced the percentage of the left ventricle occupied by fibrosis and confined the infarct region to the midmyocardium, promoting the growth of new myocardium.
6. **Cardiac Function Recovery**: MSC-treated pigs exhibited recovery of systolic and diastolic cardiac function, with improved myocardial efficiency and global cardiac performance.
These findings demonstrate that direct injection of allogeneic MSCs into damaged myocardium is a safe and effective strategy for cardiac repair, offering a promising approach for clinical application.This study investigates the use of allogeneic mesenchymal stem cells (MSCs) for cardiac repair after myocardial infarction (MI) in pigs. The researchers conducted a randomized, investigator-blinded, placebo-controlled trial to evaluate the safety and efficacy of intramyocardial injection of MSCs. Key findings include:
1. **Safety and Delivery**: MSCs were safely injected into the damaged myocardium using a percutaneous-injection catheter 3 days after MI, with no adverse events observed.
2. **Engraftment and Cardiac Function**: MSCs resulted in long-term engraftment, reduced scar formation, and near-normalization of cardiac function. MRI imaging and histological analysis confirmed the presence and integration of MSCs into the myocardium.
3. **Allogeneic MSCs**: The transplanted MSCs were prepared from an allogeneic donor and were not rejected, offering a practical advance for widespread application.
4. **Mechanisms of Benefit**: MSCs expressed muscle-specific proteins, suggesting their differentiation into cardiomyocytes. They also stimulated endogenous cellular replication, contributing to cardiac regeneration.
5. **Impact on Infarct Size**: MSC treatment significantly reduced the percentage of the left ventricle occupied by fibrosis and confined the infarct region to the midmyocardium, promoting the growth of new myocardium.
6. **Cardiac Function Recovery**: MSC-treated pigs exhibited recovery of systolic and diastolic cardiac function, with improved myocardial efficiency and global cardiac performance.
These findings demonstrate that direct injection of allogeneic MSCs into damaged myocardium is a safe and effective strategy for cardiac repair, offering a promising approach for clinical application.