Date of Award

12-2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Gao, Bruce Zhi

Committee Member

Borg , Thomas Keith

Committee Member

Simionescu , Dan

Committee Member

Dean , Delphine

Abstract

To understand how stem cells functionally couple with native cardiomyocytes is crucial for cell-based therapies to restore the loss of cardiomyocytes that occurs during heart infarction and other cardiac diseases. Due to the complexity of the in vivo environment, our knowledge of cell coupling is heavily dependent on cell-culture models. However, conventional in vitro studies involve undefined cell shapes and random length of cell-cell contacts in addition to the presence of multiple homotypic and heterotypic contacts between interacting cells. Thus, it has not been feasible to study electrical coupling corresponding to isolated specific types of cell contact modes.
To address this issue, we used microfabrication techniques to develop different geometrically-defined stem cell-cardiomyocyte contact assays to comparatively and quantitatively study functional stem cell-cardiomyocyte electrical coupling. Through geometric confinements, we will construct a matrix of identical microwells, and each was constructed as a specific microenvironment. Using laser-guided cell micropatterning technique, individual stem cells or cardiomyocytes can be deposited into the microwells to form certain contact mode. In this research, we firstly constructed an in-vivo like cardiac muscle fiber microenvironment, and the electrical conductivity of stem cells was investigated by inserting stem cells as cellular bridges. Then, the electrical coupling between cardiomyocytes and stem cells was studied at single-cell level by constructing contact-promotive/-preventive microenvironments.

Share

COinS