Funding opportunities

Procurement of tissue samples for the generation of induced pluripotent stem cells from patients afflicted with cardiovascular diseases and diabetes.

Funding Type: 
Tissue Collection for Disease Modeling
Grant Number: 
IT1-06616
Funds requested: 
$1 816 816
Funding Recommendations: 
Not recommended
Grant approved: 
No
Public Abstract: 
Cardiovascular disease (CVD) is a complex disease with strong genetic components. It remains the leading cause of death worldwide representing 30% of all global deaths. Atherosclerosis is a common CVD that manifests in plaque formation in the vascular wall of the arteries. Progression of the disease can result in occlusion of the vessel and ischemia. Similarly, 6.4% of adults on the planet have diabetes. In the United States, 8.3% of people have diabetes and nearly 3% of all deaths are due to diabetes. In California, 7.6% of people have diabetes. The incidence of CVD in diabetic patients is 2-14 times higher than in age matched, non-diabetic patients. iPSCs hold a great deal of promise in both the fields of regenerative medicine and disease therapy. By using disease state somatic cells for iPSC generation, the iPSCs retain the genetic mutations that resulted in the disease state. The disease state iPSCs can then be differentiated into any number of different cell types to study everything from disease onset and progression to the impact of specific therapies on the afflicted cell types. All of these experiments can be performed in vitro allowing for the reduction of the number of animals needed while streamlining the progression of therapies from bench top to bedside. The overall plan of this research project is to obtain a large number of atherosclerotic and diabetic blood and tissue samples. These can then be used for iPSC generation to accelerate translational medicine.
Statement of Benefit to California: 
Cardiovascular disease (CVD) is a complex disease with strong genetic components. It remains the leading cause of death worldwide representing 30% of all global deaths. Atherosclerosis is a common CVD that manifests in plaque formation in the vascular wall of the arteries. Progression of the disease can result in occlusion of the vessel and ischemia. Similarly, 6.4% of adults on the planet have diabetes. In the United States, 8.3% of people have diabetes and nearly 3% of all deaths are due to diabetes. In California, 7.6% of people have diabetes. The incidence of CVD in diabetic patients is 2-14 times higher than in age matched, non-diabetic patients. iPSCs hold a great deal of promise in both the fields of regenerative medicine and disease therapy. By using disease state somatic cells for iPSC generation, the iPSCs retain the genetic mutations that resulted in the disease state. The disease state iPSCs can then be differentiated into any number of different cell types to study everything from disease onset and progression to the impact of specific therapies on the afflicted cell types. All of these experiments can be performed in vitro allowing for the reduction of the number of animals needed while streamlining the progression of therapies from bench top to bedside. The overall plan of this research project is to obtain a large number of atherosclerotic and diabetic blood and tissue samples. These can then be used for iPSC generation to accelerate translational medicine.
Review Summary: 
The goal of this proposal is to collect a large number of tissue samples from patients with various forms of cardiovascular disease, atherosclerosis and diabetes as well as from healthy individuals. These samples will then be transferred to other parties for derivation and banking of induced pluripotent stem cells (iPSC). It is anticipated that these iPSC would be a useful resource for studying the underlying cellular defects of these diseases as well as for drug screening. Impact and Significance - Cardiovascular disease and diabetes combined are the leading causes of death in the United States and are an enormous burden to our health care system. To the extent that iPSC-based models of these diseases will provide tools for investigating mechanisms behind these diseases and for developing new drug screens, this proposal could have significant impact. Rationale - The proposal did not take into consideration the complexity of disease definition and clinical phenotyping, and did not specify how the target diseases will be defined clinically or what diagnostic criteria would be used to identify and classify appropriate patients. This concern was viewed as a major flaw of the proposal. - The application failed to provide rigorous patient inclusion and exclusion criteria. If such decisions are left to each diagnosing physician, the criteria will be inconsistent, leading to a collection with limited scientific value. - The proposed broad disease focus, including multiple types of cardiovascular disease, atherosclerosis and diabetes, was considered a weakness of the proposal since it may preclude an in-depth study of any one disease. It was felt that studies using these lines were likely to be underpowered for identifying phenotypes specific to any one disease. Quality of the Proposed Protocols - The quality of the proposed protocols for donor consent and management of private tissue donor information was acceptable, with only minor concerns: a) No rationale was given for collecting both skin and blood samples from each patient, and b) Although it was proposed, no template language was provided in the consent form to allow for patient re-contact and re-sampling. Feasibility - There were no concerns related to feasibility. The applicant has infrastructure and relationships with physicians in place, such that it is feasible to collect the number of samples proposed. Budget - The budget for sample collection is appropriate. - There was concern about the significant cost for genotyping and associated equipment (a sequencer) and reviewers questioned whether this genotyping work is necessary for the proposal. Qualifications of the Principal Investigator (PI) and Team Members, Resources - The team is well qualified to do the tissue collection, but it is a major oversight not to include a geneticist and clinical experts in cardiac disease and diabetes on the team.
Conflicts: 

© 2013 California Institute for Regenerative Medicine