Collection of Human Placenta-derived Amniotic Mesenchymal Stem Cells to Model Tetralogy of Fallot

Funding Type: 
Tissue Collection for Disease Modeling
Grant Number: 
IT1-06575
Investigator: 
ICOC Funds Committed: 
$0
Public Abstract: 
Congenital heart defects (CHD) are among the most common birth defects, and account for the largest proportion of infant mortality due to birth defects. Despite its common occurrence, genetic complexity, important clinical symptoms, and possible environmental effects, investigation of the mechanism of CHD has lagged far behind adult cardiovascular disease. Absence of specific disease classification and lack of clear understanding of this serious newborn problems have resulted in poor diagnosis and therapy of CHD. Tetralogy of Fallot (ToF) is the most common type of severe CHD with highly consistent symptoms and known association with genetic abnormality. The occurrence of ToF in California, the US, and worldwide is approximately 1 in 2,000 live births making this the most common type of CHD requiring surgery. In this proposal, a multi-disciplinary effort, including geneticists, pediatricians, computer scientists, cardiologists, peri-natologists, and stem cell biologists, will study the modified cells generated from patients with ToF. A robust and innovative platform, employing the placenta-derived stem cells from ToF infants, will allow non-invasive generation of modified cells (induced pluritotent stem cells, iPSCs) and modified (iPSC-derived) heart cells. [REDACTED] is a national referral center for ToF. We propose to collect 40 ToF and 20 normal placentas per year.
Statement of Benefit to California: 
The prevalence of tetralogy of Fallot (ToF) in California is approximately 1 in 2,000 live births making this the most common type of serious congenital heart disease requiring surgery. Congenital heart defects (CHD) are among the most common birth defects, and results in the largest proportion of infant mortality due to birth defects. Despite the common occurrence of CHD and their complex clinical findings, investigation of CHD has lagged far behind adult cardiovascular disease. Absence of well-defined disease classification and lack of clear understanding of this serious newborn problems have resulted in poor diagnosis and therapy. The proposed investigation of ToF may address the criticcal issues in studying CHD. The anatomic abnormalities of ToF are more consistent and better defined. Specific genetic abnormalities associated with ToF have also been identified. In this proposal, a multi-disciplinary collaboration among doctors and scientists from different fields will study iPSCs generated from patients with ToF. A reliable platform, employing the placenta-derived stem cells from ToF infants, will allow non-invasive, patient-specific generation of iPSCs and iPSC-derived cardiomyocytes. [REDACTED] is a national referral center for ToF. We are confident that we wil be able to collect 40 ToF placentas per year as described in our proposal.

© 2013 California Institute for Regenerative Medicine