Human cardiac tissues have limited regenerative capacity. Damage in cardiac tissues from ischemia or other pathological conditions can result in heart failure, the leading cause of death in the United States. In addition, cell loss or dysfunctin in pacemaker tissues due to congenital heart defects, aging, and acquired diseases that damage the conduction system can cause severe arrhythmias. Human pluripotent stem cells hold great promise for cardiac cell therapy. These cells can be differentiated into nodal and working (atrial and ventricular) cardiac subtypes, which are suitable for different applications: enriched working-type cells without the contamination of nodal-type cells for repairing injured ventricular myocardium, and enriched nodal-type cells for developing a biological pacemaker. However, none of the existing methods can generate homogeneous cells for a specific subtype, and methods for the isolation and enrichment of each subtype have not been well developed. Research on cardiac subtype specification has been challenging due to the lack of an analysis tool that can be used in a throughput platform to distinguish and enrich cardiac subtypes. This R21 proposal aims to track, enrich and characterize cardiac subtypes using a novel nanotechnology based tool without genetically modifying the cells. This technology will allow us to generate highly homogeneous nodal- or working-type cell populations and therefore facilitate future applications of human pluripotent stem cells in cardiac cell therapy. It can also help accelerate studies to understand the regulation of cardiac subtype specification from human pluripotent stem cells.

Public Health Relevance

Cardiac cell therapy has the potential to treat heart failure from the loss of cardiomyocytes (heart cells) and arrhythmias from impaired pacemaker activity. A promising source of cells for cardiac cell therapy is the cardiomyocytes generated from human pluripotent stem cells. This study aims to track, enrich and characterize specific cardiac subtypes needed for cardiac regeneration or the development of biological pacemakers using a novel nanotechnology based tool.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL118454-01
Application #
8491581
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Buxton, Denis B
Project Start
2013-06-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$233,686
Indirect Cost
$80,559
Name
Emory University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Li, Yan; Xu, Chunhui; Ma, Teng (2014) In vitro organogenesis from pluripotent stem cells. Organogenesis 10:159-63
Nguyen, Doan C; Hookway, Tracy A; Wu, Qingling et al. (2014) Microscale generation of cardiospheres promotes robust enrichment of cardiomyocytes derived from human pluripotent stem cells. Stem Cell Reports 3:260-8