Takeyoshi Ota, MD, PhD

CARDIAC, THORACIC AND VASCULAR

Overview:

Basic research projects

1. Controlled Growth Factor Releasing Bio-Cardiac Patch for Myocardial Regeneration

Heart failure is a major health problem with increasing prevalence, caused in part by the increased survival for patients who have had acute myocardial infarction, increased life expectancy, and lifestyle choices. Post-infarction left ventricular remodeling is characterized by ventricular dilatation and abnormal geometry including development of ventricular aneurysm leading to congestive heart failure. There are about 53,000 deaths per year related to congestive heart failure. Although heart transplantation is currently the best surgical option for the treatment of severe heart failure, it only serves for about 2,000 patients per year in the United States due to a shortage of donors. Mechanical support technologies such as left ventricular assist device have been developed to compensate for the lack of available donor organs. However, this therapy is limited by infection, cost, durability, and thromboembolism.

In an effort to provide more treatment options and improve the clinical outcomes of advanced heart failure patients, we are developing new tissue-engineered cardiac patch materials that enhance the in-situ regeneration of functional myocardial tissues. Based on our preliminary studies, one of the most promising tissue-engineered materials for the cardiac patch is decellularized extracellular matrix (ECM) that serves as a bio-scaffold to house site-specific host cells, leading constructive tissue regeneration. 

Our latest ECM cardiac patch is enhanced with controlled release of a growth factor to promote in-situ regeneration and is being under animal studies. At the conclusion of the project, we believe that we could provide an efficient and safe biocompatible material for myocardial regeneration, which we believe lead to potentially save over 50,000 severe heart failure patients who die annually despite maximized medical therapy.

2. Regression and Prevention of Aortic Aneurysm with Controlled Release of a Biochemical Agent

Aortic aneurysm is characterized by localized structural deterioration of the aortic wall that will eventually lead to dissection or rupture. At present, pharmacologic therapy has not yet been established for treating aneurysm, and standard treatment is limited to open surgical or endovascular repairs. The challenges with these interventions include significant invasiveness, non-negligible operative mortality, and procedure related complications. Ideally, non-invasive therapy for aortic aneurysm is desired.   

Our group has developed reproducible abdominal aortic aneurysm (AAA) animal model to facilitate the research of aortic aneurysm, and demonstrated that inhibition of reactive oxygen species was crucial in both the prevention of aneurysm formation and expansion of AAA. In addition, we found that prolonged topical delivery of a biochemical agent prevented aneurysm formation and reinforced aortic wall. 

We are currently under a proof-of-concept study in an animal model to prove effectiveness of our material. Our long-term goal is to apply this technique to treat human aortic aneurysm in clinical practice. 

Clinical Research Projects

1. Single Dose Del Nido Cardioplegia Solution, Safety and Efficacy for Myocardial Protection
2. Aortic Root Aneurysm and Reconstruction, Clinical outcomes
3. Preoperative functional assessment using the Frailty Scoring System for patients with end-stage heart failure undergoing left ventricular assist device and heart transplant surgery
4. Clinical outcomes of Jehovah's Witnesses in Cardiac Surgery
5. Clinical Trials, Ventricular assist device related (PREVENT trial, ENDURANCE trial etc.)