Publication Date

2011-04-08

Availability

Embargoed

Embargo Period

2012-04-07

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2011-03-30

First Committee Member

Herman S. Cheung

Second Committee Member

Fotios Andreopoulos

Third Committee Member

Chun-Yuh Huang

Fourth Committee Member

Ian K. McNiece

Abstract

The application of cellular therapies for the treatment of myocardial infarction has provided encouraging evidence for the possibility of cellular therapies to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. Here I propose the use of a unique population of stem cells arising from the embryonic neural crest. These cells were shown to express neural crest markers as well as pluripotency-associated markers. Furthermore, the cells were shown to express proteins essential to the formation of gap junctions and to possess a cardiomyogenic differentiation potential by several means. Furthermore, I explore the use of mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for the better engraftment of the cells while in the heart. Mechanical strain was shown to elicit a cardiomyogenic response from the cells following just a couple of hours of stimulation. The mode in which mechanical strain elicited these responses was demonstrated to be via the mediation of the reactive oxygen species (ROS) pathways. Given the results presented here, the use of these periodontal ligament-derived stem cells (PDLSC) in combination with mechanical strain preconditioning of the cells prior to their delivery into the heart may pose a valuable alternative for the treatment of myocardial infarction and merits further exploration for its capacity to augment the already observed beneficial effects of cellular therapies.

Keywords

Stem Cells; Cardiomyogenesis; Mechanical Strain; Mechanotransduction

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