- Title Information
- Title
- Modeling Development and Disease In Human Engineered Cardiac Tissue
- Name:
Personal
- Name Part
- Rupert, Cassady Elise
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Coulombe, Kareen
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Black, Lauren
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Colvin, Vicki
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Hurt, Robert
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Mathiowitz, Edith
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Mende, Ulrike
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biomedical Engineering
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2019
- Physical Description
- Extent
- xii, 184 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Ph. D.)--Brown University, 2019
- Genre (aat)
- theses
- Abstract
- Cardiovascular engineering using human pluripotent stem cell (hPSC)-derived cardiomyocytes holds incredible potential for disease modeling, therapeutic development and testing, and cardiac regeneration. The heterogeneity and plasticity of hPSCs and hPSC-cardiomyocytes can be both assets and obstacles to the generation and advancement of new technologies, and a deeper understanding of how to manipulate these cells is needed. The research pursued in this dissertation explores novel means to engineer healthy and diseased states in hPSC-cardiomyocytes from the single-cell to tissue level. Studies were performed using a broad scale of metrics including cell and tissue structure, gene expression, bioenergetic phenotype, and electromechanical function in order to obtain a fuller picture of hPSC-cardiomyocyte response to mechanical, biochemical, and cellular stimuli. Important and novel findings show that (1) confocal microscopy imaging of single cells reveals hPSC-cardiomyocyte contractile lattice and cytosolic volume respond independently to hypertrophic stimulation; (2) developmental growth factors stimulate proliferation and metabolic maturation of hPSC-cardiomyocytes in engineered tissues; (3) adult human cardiac fibroblasts can be manipulated to produce physiological and pathophysiological phenotypes in engineered tissues; and (4) metabolic selection to purify hPSC-cardiomyocyte populations changes bioenergetic phenotype. Taken together, these results stress the importance of considering hPSC-cardiomyocyte immaturity and plasticity in engineered cardiac tissues, and that, because of these features, hPSC-cardiomyocytes provide unexpected avenues for engineering development and disease in the dish.
- Subject
- Topic
- tissue engineering
- Subject
- Topic
- induced pluripotent stem cells
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/01765419")
- Topic
- Embryonic stem cells--Research
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00953714")
- Topic
- Heart cells
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20200720
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations