Abstract 12030: Fibrin Patch-Based Transplantation of Pim-1 Engineered MSC Improves Cardiac Function of Swine Hearts with Post-Infarction LV Remodeling
Background: The serine-threonine kinase Pim-1 regulates cellular proliferation and survival with cardioprotective effects when expressed in transgenic mice. However, the ability of Pim-1 engineering in mesenchymal stem cells (MSC) has never been explored, nor has the efficacy of Pim-1 expressing cells been tested in a large animal model of infarction injury. In this study, we aim to explore the therapeutic potential of Pim-1 engineered MSC for cardiac repair in a swine model.
Methods and Results: Mesenchymal stem cells (MSC) obtained from swine bone marrow were engineered to over express Pim-1 and GFP (pMSC) or GFP only (cMSC). Higher proliferation rate and better resistance against serum free and hypoxia-induced apoptosis were observed for pMSC compared to cMSC in vitro. The MSCs were tested in a swine model of post-infarction LV remodeling to examine the therapeutic potential. Briefly, female farm pigs underwent coronary artery occlusion of 60 min followed by reperfusion. Animals were randomized to receive saline (MI, n=6), fibrin patch vehicle (MI+P, n=6), fibrin patch seeded with 10 million cMSCs (cMSC, n=4) or fibrin patch seeded with 10 million pMSCs (pMSC, n=4). Animals were followed up for one month and cardiac function was measured with clinic 1.5 Tesla MRI at one week and 4 weeks post surgery. At one week post surgery, a moderate improvement of global cardiac function in terms of ejection fraction (EF) was observed in both cell transplanted groups (p=NS vs MI). However, a significant improvement of regional thickening fraction in the infarct zone was observed (p<0.05 vs MI). At one month post surgery, beneficial effects from either type of MSC transplantation persist. In addition, both types of MSC transplantation attenuated cardiac hypertrophy indexed as left ventricular weight over body weight (p<0.05 vs MI). Noticeably, the pMSC group demonstrated a further significant improvement of ejection fraction compared to cMSC group (52.7±3.6 vs 45.2±3.2 p<0.05).
Conclusion: Pim-1 engineering of MSC augments efficacy in a large animal model of infarction, indicating that this cardio-protective molecular target that can be utilized and manipulated for therapeutic strategies.
- © 2011 by American Heart Association, Inc.