Drug- and cell-based strategies for treating heart disease, including myocardial infarction, face significant roadblocks on the path to the clinic, a primary obstacle being the lack of information-rich in vitro human model systems. Conventional model systems are hampered by at least one of three fundamental limitations which include a) the lack of an in vivo-like microenvironment specifically engineered for the input cell population, b) a relatively low-throughput assays, and c) the low-content nature of output parameters. We describe an integrated computational, design, and experimental strategy for the rational design of a microfabricated high-content screening platform which we term the Cardiac MicroWire (CMW) system. Within this system, we recapitulate the basic microenvironment found in the heart, one which integrates cardiomyocytes, non-myocytes, the extracellular matrix, and dynamic electromechanical forces. Our results highlight the CMW system’s potential as a powerful discovery tool for screening small molecules and transplantable cells toward heart regeneration therapies.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32494 |
| Date | 23 July 2012 |
| Creators | Thavandiran, Nimalan |
| Contributors | Zandstra, Peter W., Radisic, Milica |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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