Engineered Development: Human Cardiac Developmental Tissue Model for Multifactorial Screening for the Onset of Congenital Heart Defects
Abstract
The proposed project addresses the Fiscal Year 2019 Peer Reviewed Medical Research Program Topic Area of “Congenital Heart Disease.” It is relevant to the areas of encouragement as it is “research to improve the understanding of the causes of congenital heart defects,” and also as it “designs and implements a disease-in-a-dish model.” The heart is the first organ to be developed in the embryo and it starts out as a simple tube. This tube undergoes a phenomenon that causes it to fold and loop over itself, resulting in the formation of the normal adult four chambered structure for the organ. Normal folding causes the heart to fully develop; however, an interruption in this phenomenon can cause for malformations of the heart known as congenital heart disease (CHD). CHD’s permanent malformations of the heart require major surgeries for the child for the duration of their lives. In the most extreme cases, CHD can result in the death of the child. CHD is a fairly common issue, occurring in approximately 1.35 million births every year, signifying it as a major heath concern and a societal burden. There are three main factors that can cause CHDs to form. These factors are described as being genetic, chromosomal, or environmental due to toxic agents. There is a very limited understanding for which specific factor corresponds to different specific CHDs. In fact, the leading cause of CHDs are through different factors combining together where the specific roles each individual factor is not well understood. Therefore, there is a critical need for a model system to better understand the cause of CHD and the roles that the different factors have in creation of malformations of the heart. In this project, we propose to create a tissue model of CHD by combining the principles of tissue engineering and developmental biology. The proposed tissue model will be treated with different toxic agents known to create CHDs in the body including alcohol, cigarette smoke, and the psychiatric drug lithium. We will look to understand whether these toxins affect heart tissue formation and their role on the genetic makeup of different heart cell types. This proposed research would be the first three-dimensional tissue model that can act as a disease-in-a-dish model of CHD. The proposed model will be useful going forward as a way to potentially predict the formation of CHD, act as a toxin screening model for the formation of CHD, and act as a drug screening model to help treat CHD in the future.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010193
Entities
People
- Harald Ott
Organizations
- Massachusetts General Hospital
- United States Army