Abstract 1635: Mesenchymal Stem Cell Therapy Prevents Ischemia/Reperfusion Injury
Ischemic heart disease, especially myocardial infarction, is an important cause for heart failure. However, therapeutic potential of mesenchymal stem cells (MSC) for myocardial or pulmonary ischemia/reperfusion (IR) injury is not well studied. MSC were tested for their ability to prevent warm IR injury.
Methods: Bone marrow cells from Lewis rat were cultured in plastic tissue culture flasks for 72 hours; cells in suspension were discarded and the adherent cells (MSC) were expanded. Experimental design: following 120 minutes of left lung ischemia, Group A, rats received MSC (~2 x 106; i.v.; passage 2– 6); Group B, rats received fibroblasts (~2 x 106; i.v.) ; Group C, received saline; and Group D received no ischemia or MSC. Left lung ischemia was performed by clamping left pulmonary artery/vein/bronchus at end inspiration. At 4h, 24h and 72h following ischemia, blood was collected from left and right pulmonary veins, separately.
Results: Mean blood oxygenation (PaO2/FIO2 ratio, mmHg) at 24h was significantly (P < 0.05) reduced following IR injury in Group B (104 ± 124; n = 6) and Group C (87 ± 39; n = 10) compared to MSC treated Group A (454 ± 59; n = 6). In sham operated controls (Group D) it was 491 ± 24 (n = 5). Significant improvement in lung oxygenation with MSC therapy was observed as early as 4h (305 ± 37; n = 6) in MSC treated animals compared to untreated controls (63 ± 19; n = 6). Histopathology of IR injured lungs (at 4 h reperfusion) demonstrated significantly (P < 0.05) reduced injury score (Grade 1.1 ± 1; n = 7) with MSC therapy compared to untreated controls (Grade 2.5 ± 1.4; n = 6). Inflammatory mediators MCP-1, TNF-α, and IL-6 protein levels were significantly (P < 0.05) reduced in MSC treated lungs compared untreated controls. Bronchoalveolar lavage at 24h post-MSC therapy demonstrated reduced (P < 0.05) inflammatory cells (granulocytes) compared to untreated controls. Wet to dry ratio and microvascular permiability index of the IR injured lungs were markedly reduced with MSC therapy. Ex vivo expanded MSC (passage 2) were highly positive for stem cell markers CD29, CD90, and CD44 (70–95%) and weakly positive for CD31, CD45 and CD11b (6 –24%).
Conclusions: Autologous MSC therapy to prevent IR injury and improve lung function in cardiopulmonary diseases seems promising.