Introduction. Myocardial infarctions occur when blood supply to a section of the heart is blocked, most often due to coronary thrombosis, leading to ischemia and death of cardiac muscle tissue. Once the tissue dies, a scar is formed, and the damage is permanent, resulting in decreased mechanical function, which can lead to heart failure. Although there are many effective reperfusion therapies such as PCI and t-PA, they can only prevent further damage and cannot regenerate dead myocytes.1 Stem cell therapy is currently being studied to regenerate dead myocytes in patients with ischemic damage. A major limitation in stem cell therapy is the low survival rate of transplanted stem cells in the hypoxic environment of ischemic tissue.2 Hypoxia-preconditioned mesenchymal stem cells (MSCs) show improved survival and regeneration potential. Recent studies suggest a variety of genetic changes which alter the expression and secretion of proteins and growth factors in response to stress from hypoxia are the leading cause of their success. Methods. Mesenchymal stem cells harvested from rats were incubated in 1% O2 for 24 hours.3 Expression of cardiomyogenic factors,4 homing and cell adhesion proteins,5 growth and angiogenic factors,6 and anti-apoptotic proteins7 were compared in preconditioned and normal MSCs. Myocardial infarctions were induced in rats by surgical occlusion of the left anterior descending artery, and stem cells were injected into the infarcted myocardium.5 Echocardiograms were performed on treated and untreated models to compare cardiac function, and hearts were harvested to histologically compare scar size and viable cardiac tissue between the different treatments.5,6,8 Results. Preconditioned MSCs express a greater number of cardiomyogenic4 and cell adhesion genes (p<0.05 & p<0.01) and show increased adhesion to areas of infarction (p<0.001).5 They were also shown to decrease the production of collagen and scar tissue in areas of ischemia, increase expression of growth and pro-angiogenic factors (p<0.05),6 and decrease apoptosis of the transplanted stem cells (p<0.01).7 Cardiac function (ESV, EDV, %EF, and LV thickness) improved in hearts treated with preconditioned MSCs (p<0.001).5 Conclusion. Hypoxia-preconditioned mesenchymal stem cells show promising results for regeneration of infarcted cardiac tissue in the treatment of MI. Exposure to hypoxia has proven to be an efficient and effective way to improve survival of transplanted stem cells. Although further research needs to be done on human models, current studies show that preconditioned MSC therapy is a safe and practical option for the treatment of MI.
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- Irfan K, Anwar A, Muhammad AA, et al. Preconditioning of mesenchymal stem cells with 2, 4-dinitrophenol improves cardiac function in infarcted rats. 2016. doi: 10.1016/j.lfs.2016.08.014.
- Hu X, Yu SP, Fraser JL, et al. Transplantation of hypoxia-preconditioned mesenchymal stem cells improves infarcted heart function via enhanced survival of implanted cells and angiogenesis.The Journal of Thoracic and Cardiovascular Surgery. 2008;135(4):799-808. doi: 10.1016/j.jtcvs.2007.07.071.
- Bader AM, Klose K, Bieback K, et al. Hypoxic preconditioning increases survival and pro-angiogenic capacity of human cord blood mesenchymal stromal cells in vitro.PloS one. 2015;10(9):e0138477. doi: 10.1371/journal.pone.0138477.
- Hu X, Xu Y, Zhong Z, et al. A large-scale investigation of hypoxia-preconditioned allogeneic mesenchymal stem cells for myocardial repair in nonhuman primates: Paracrine activity without remuscularization. Circulation Research. 2016;118(6):970-983. doi: 10.1161/CIRCR