Date of Award
Master of Science (MS)
The irreversible damage to the heart caused by myocardial infarction (MI) leads to over one million deaths in the United States every year. There are several approaches to treat MI, such as angioplasty, redirected blood flow, and electrical medical devices, but they cannot promote new cardiac tissue generation, thus leading to potential high risk of re-surgeries. To overcome this limitation, stem cell therapy is regarded as a promising method. However, the implantation of stem cells has ethical and safe concern and the efficiency is limited due to low cell engraftment. Moreover, the effect of stem cell is predominantly attributed to paracrine effect. Therefore, the delivery of stem cell secretome is expected to be a prominent approach, since it has potential to achieve similar effect without causing safety and ethical problems with cell implantation. Among different cells, cardiac fibroblast (CF) is the largest cell population in the heart, and its secretome has been shown to protect cardiomyocytes under hypoxia. Thus, the objective of this work is to deliver CF secretome to the heart after MI. In the first part of this thesis, CF secretome was optimized in vitro by adjusting environmental oxygen condition and substrate stiffness. We found that the secretome collected under hypoxic condition (1% O2) and soft substrate (6 kPa) can most effectively boost the survival of endothelial cells and cardiomyocytes under hypoxia. In the second part, we developed platelet-membrane coated nanoparticles as a delivery vehicle for CF secretome. The nanoparticles had the capability of sustainedly releasing various growth factors such as PDGF, VEGF and bFGF. This secretome delivery system has potential to promote cardiac repair after MI.
Jianjun Guan Dennis Barbour Nathaniel Huebsch