Platelet-endothelial interactions play a vital role in diseases such atherosclerosis and ischemic injury such as myocardial infarction. Vascular injury/inflammation after MI can lead to platelet activation and trafficking, up- regulations of adhesion molecules, and production of reactive oxygen and nitrogen species in vasculatures. Despite in many cases platelet activation is harmful, recent studies indicate that after ischemic injury circulating stem cells (release from the bone marrow) rely on platelets to navigate into the injured heart for tissue repair. Platelets form co-aggregates with circulating stem cells in patients with myocardial infarction and thereby increase peripheral recruitment within the ischemic microcirculatory district and promote adhesion to the vascular lesion to promote healing. For the last decade, we have been working in the field of stem cell therapy for post-injury cardiac repair. One big challenge is to target infused stem cells to the cardiac injury site. Poor cell engraftment in the heart may at least partially explain the none-to-marginal efficacy of stem cell therapies for heart diseases so far. We hypothesize that expression of platelet binding motifs on stem cells can help them target to the injured heart. We devised a method of adding platelet binding motifs onto stem cells without genetically altering the cells. Instead, transient expression can be achieved by cell fusion mechanisms. We will first generate platelet membrane vesicles from live platelets and then decorate these vesicles onto the surface of therapeutic stem cells. This method is robust and simple. Under the auspice of this grant study, we aim to evaluate the cytotoxicity of this approach on stem cell functions and test the safety/efficacy of this approach to enhance endogenous and exogenous stem cell therapies in animal models of myocardium infarction.

Public Health Relevance

Platelet activation and trafficking can lead to cardiovascular diseases but the interaction of platelet with circulation stem cells is beneficial in post-injury repair. We plan to harness the binding ability of platelets to transport injected stem cells into the injured heart. This approach can potentially enhance delivery efficiency thereby augmenting the therapeutic benefits of stem cells.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL144002-02
Application #
9882324
Study Section
Myocardial Ischemia and Metabolism Study Section (MIM)
Program Officer
Bai, C Brian
Project Start
2019-04-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695