The use of biomaterials for stem cell therapies to prevent myocardial damage post-infarct

This thesis employed a stem cell encapsulating hydrogel patch to increase the amount of beneficial soluble factors that are delivered to the surface of damaged heart tissue following a myocardial infarction. While current medical practices to address the immediate aftermath of a myocardial infarction (MI) have evolved tremendously, there are few, if any, techniques currently administered to slow, cease, or reverse the negative side effects of an occluded artery, such as the replacement of functional myocardium with non-contractile scar tissue. Because of this scar formation, survival of the initial heart attack is commonly accompanied by a decrease in left ventricular functioning due to wall thinning and ventricular enlargement. As a result of the slow, or absent, ability of cardiomyocytes to divide and repopulate the infarcted area, the burden of heart function lies on the surrounding tissue; a load that exhausts the healthy tissue and decreases the quality of life of heart attack survivors. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic avenue for post-MI treatment, in part due to the “survival signals” that they secrete. Previous work has shown that by increasing the amount of “survival signals” that are introduced to the damaged myocardium, the extent of cardiomyocyte cell death, and subsequent scar formation, can be decreased. While the therapeutic effects of these factors have been documented, one difficulty lies in the ability to maintain a constant flux of secreted factors to the damaged site. This project hypothesized that through the encapsulation of stem cells within an engineered hydrogel construct, the hurdle of soluble factor delivery at the site of injury could be overcome. A constant flux of paracrine factors to the heart surface would allow for cell recruitment to the site(s) of damage, prevention of tissue degradation due to inhospitable environments, and promotion of neovascularizion for sustainable tissue regeneration. Using both a chick chorioallantoic membrane assay and a mouse model of MI, the following aims determined: 1) the vascularization potential of an MSC encapsulated patch, 2) the ability to deliver hydrogels containing pro-survival signals to the heart post-MI, and 3) the ability of these factors to decrease scar formation and improve cardiac function following a heart attack. Knowledge gained from this project will provide the basis for designing materials and strategies for similar studies in larger animal models and eventually for human clinical trials. Successful delivery of the MSC encapsulating patch, and subsequent decrease in myocardial degradation, will greatly improve the quality of life scores of individuals who have suffered heart failure. This increase in quality of life will aid in post-MI mobility and decrease the need for more intensive health care following the initial heart attack; overall decreasing the burden a strained heart has on both patients and the healthcare system.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Melhem, Molly Rami

Contributors dc:contributor

• Schook, Lawrence
• Kong, Hyun Joon
• Bashir, Rashid
• DiPietro, Luisa

• Stem cell therapy
• myocardial infarctions
• tissue engineering
• biomaterials

Statement dc:rights

• Copyright 2015 Molly Melhem

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/78766

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/78766