Overcoming Immunological Barriers for Preclinical Studies of Cardiac Stem Cell
Abstract
Ischemic cardiomyopathy is a condition where the heart muscle weakens due to inadequate blood flow. This can lead to permanent damage and eventually heart failure. This condition is the leading cause of death and affects millions of individuals in the United States. Current medical therapies are beneficial; however, none has been proven effective in preventing development of heart failure. The potential of human embryonic stem cells (hESCs) to self-renew and become heart cells makes them a valuable cell source for transplantation into the injured heart. But before hESCs can be used in patients, further studies are needed to: (1) identify and purify specific types of heart cells arising from hESCs, (2) provide a supportive environment for the cells to grow during and after transplantation, and (3) determine ways to bypass the host immune system, which normally recognizes and destroys foreign pathogens or external cell sources such as hESCs. Our research focuses on a labeling strategy to generate and isolate specialized heart cells from hESCs at different stages of development. This is an important strategy in maximizing the safety and efficacy of cell transplantation, as previous studies have used a mixed cell population, which limits their clinical application and poses the risk of causing abnormal heart arrhythmias. A novel aspect of our proposal is the use of a cell line that does not elicit an immune response, thereby preventing massive cell loss due to recognition and clearance from immune cells. This also holds great clinical significance as the cost and side effects of immunosuppressive drugs for patients after cardiac transplantation are of concern. Additionally, as a potential way to improve the number of cells that survive after transplantation, we propose to mix our cells with an oxygen-generating gel. One of the current problems with transplantation is that there is not enough oxygen in the heart after injury and many of the transplanted cells die before they can help to restore the heart muscle. This gel would provide oxygen and mechanical support to our cells. We propose to use this non-immunogenic cell line to generate specialized heart cells that can be incorporated into an oxygen-generating gel for proof-of-concept studies in a rat heart attack model. We will use an imaging modality called echocardiography to examine whether injection of these cells will improve cardiac function after injury. Finally, we will determine the effectiveness of these cells in evading the host immune system using staining to identify the number of immune cells that gets recruited to the injection area. The successful completion of our proposal would help to push the field of cell transplantation closer to clinical application, where it would be able to alleviate the pain and financial burden of heart disease for many Americans. We believe that our generation of specialized heart cells that can evade the immune system, along with an engineering approach to develop an oxygen-generating gel to support cell health, addresses the current major concerns with cell transplantation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910244
Entities
People
- Arash Pezhouman
Organizations
- United States Army
- University of California, Los Angeles