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DOI: 10.1055/s-0030-1269115
Dysregulation of pro-angiogenic factors results in failure of the hypertrophied heart
Objectives: Stem cell-transplantation is a promising treatment strategy for cardiac regeneration in cardiomyopathy. Paracrine factors from bone marrow stem cells have pro-angiogenic and anti-apoptotic effects on the myocardium, resulting in increased myocardial perfusion and enhanced function. Here, systemic bone marrow mononucleated cell (MNC) transplantation is investigated for its regenerative potential in a mouse model of cardiac hypertrophy.
Methods: Left-ventricular (LV) hypertrophy was induced by transoartic constriction (TAC) in NOD-scid mice. Human bone marrow was processed by Ficoll gradient-centrifugation. The cell product was characterized by FACS analysis (CD34, CD45, CD133) and colony forming units (CFU). 1×10e6 MNC were transplanted intravenously 1 week post-TAC (n=15). Cardiac-MRI assessment was performed weekly and included determination of myocardial perfusion-indices (MPI), LV-volume, wall-thickness and ejection-fraction. Capillary density was determined by quantitative immunohistochemistry (Caveolin 1).
Results: Human bone marrow MNC for transplantation were verified by FACS analysis and gave rise to 12.3±2.7 CFU per million cells. MPI by MRI was reduced in TAC-mice compared to Sham, where MNC-transplantation resulted in restoration of MPI (4.2±1.3 (Sham); 1.9±0.8 (TAC); 3.9±1.1 (MNC, p=0.007 vs. TAC)) confirmed by capillary density assessment (4538±383 (Sham); 3587±376 (TAC); 4253±334 (MNC, p=0.021 vs. TAC)). However, while onset of heart-failure was delayed, there was no change in LV-wall-thickness.
Conclusions: Bone marrow MNC transplantation induces proangiogenic effects non-ischemic cardiomyopathy with a significant delay of onset of heart-failure. These promising results can be easily translated into clinical application a have a significant benefit for patients with non-ischemic heart-failure.