Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioengineering

Committee Member

Dr. Dan Simionescu, Committee Chair

Committee Member

Dr. Agneta Simionescu

Committee Member

Dr. Ken Webb

Abstract

In the United States, 900,000 people a year experience myocardial infarction (MI), making it the leading cause of death. Current treatment options such as coronary artery bypass procedure (CABG) and percutaneous coronary intervention (PCI) minimize damage to the myocardium, but do not guarantee restoration of blood flow and are associated with other complications such as renal failure. Heart transplants remain the sole existing therapy to restore cardiac function, but are limited by donor availability and chronic immune response. Many research groups have turned to tissue engineering to provide a strategy that restores function to the heart.

Our solution is to create an acellular myocardial scaffold seeded with the patient’s own cells, which will be implanted to replace ischemic myocardium and restore function to the heart. The goal of this study is to re-endothelialize the vasculature of the left coronary artery and its surrounding branches and capillaries. This will provide the vasculature needed to sustain a tissue engineered construct. First, rabbit hearts were prepared using an SDS based perfusion decellularization protocol. The produced scaffolds were then analyzed for preservation of the vasculature pathways beginning at the left coronary artery, and for removal of cellular components and retention of ECM components. Next, human aortic endothelial cells (ECs) and human adipose derived stem cells (ADSCs) were injected into the left coronary arteries of the hearts in order to test the ability of the cells to attach to the lumen of the acellular vessel walls.

The perfusion decellularization procedure resulted in complete preservation of the vasculature pathway beginning at the left coronary artery and ending in the corresponding vein. The scaffold was proven to be acellular and to have retained basic components of collagen and elastin. Hearts seeded with either ECs or ADSCs were found to have cells adhered to the walls of the vasculature, proving that both cell types are viable options for complete re-endothelialization of coronary vasculature in decellularized rabbit heart models.

This research will add to the effort of creating an alternative therapy to heart transplants using human donors for patients suffering from post-MI complications. It will also advance the field of cardiovascular tissue engineering, by being the first study to both utilize rabbit heart models for xenogenic recellularized constructs, and utilize stem cells as a possible cell source for re-endothelialization of the coronary vasculature.

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