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Published on: March 1, 2016
Bone marrow cell-induced protection of the human myocardium: characterization and mechanism of action
Vien Khach Lai1, José Linares-Palomino, Bernardo Nadal-Ginard
1Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
Insights
Bone marrow cells protect the heart by releasing factors that activate the insulin-like growth factor-1 receptor. This finding offers new therapeutic strategies for ischemic heart disease.
Area of Science:
- Cardiology
- Regenerative Medicine
- Cell Biology
Background:
- The cardioprotective mechanisms of bone marrow cells are not fully understood.
- Investigating these mechanisms is crucial for developing novel therapies for heart disease.
Purpose of the Study:
- To elucidate the protective effects of bone marrow cells on human myocardium.
- To identify the underlying molecular mechanisms involved in this protection.
Main Methods:
- Human myocardial tissue and bone marrow cells were obtained from cardiac surgery patients.
- Simulated ischemia-reperfusion injury models were used to assess myocardial damage.
- Creatine kinase release, necrosis, and apoptosis were quantified to measure injury.
Main Results:
- Autologous bone marrow cells significantly reduced myocardial injury by 70-80%.
- Allogeneic cells, cryopreserved or cultured cells, provided similar protection.
- Protection was mediated by secreted factors acting through the insulin-like growth factor-1 receptor.
Conclusions:
- Bone marrow cells exhibit potent cardioprotective properties.
- The protective effect is mediated by secreted factors and the insulin-like growth factor-1 receptor.
- These findings have significant implications for treating ischemic heart disease.
Objectives:
The mechanism of the putative beneficial effect of myocardial transplantation of bone marrow cells remains unclear. We studied the protective properties of bone marrow cells on the human myocardium and investigated the underlying mechanism.
Methods:
Bone marrow cells and the right atrial appendage were obtained from patients undergoing elective cardiac surgery. Myocardial slices were subjected to 90 minutes of simulated ischemia/120 minutes of reoxygenation at 37 degrees C following various protocols. Tissue injury was assessed by creatine kinase released into the media during the reoxygenation period, and myocardial necrosis and apoptosis were determined by propidium iodide and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (percent of aerobic control).
Results:
Autologous unfractionated bone marrow cells significantly reduced myocardial injury. Maximal protection was obtained with 5 x 10(6) autologous cells (approximately 1.5 x 10(5) cells/mg wet myocardium) that caused a reduction in creatine kinase release and cell death by necrosis and apoptosis of 70% to 80%. Allogenic bone marrow cells were as protective as the autologous cells and their effect was unaffected by prior frozen storage or culturing. Similar myocardial protection was also attained when bone marrow cells were present only before or during ischemia, or during reoxygenation, a benefit that was comparable with that of ischemic preconditioning. Conditioned media by the bone marrow cells was sufficient to induce protection, which was abolished by the selective insulin-like growth factor-1 receptor blocker PQ401.
Conclusions:
Bone marrow cells possess potent myocardial protective properties that are triggered by a secreted factor or factors and mediated by insulin-like growth factor-1 receptor. These results have important clinical implications for the therapeutic use of bone marrow cells in ischemic heart disease and for the design of future clinical studies.
