Cardiac extracellular matrix gel for ESC-derived cardiomyocyte maturation

Thompson, Madalynn Jade

Cardiac extracellular matrix gel for ESC-derived cardiomyocyte maturation

dc.contributor.advisor	Rancourt, Derrick E.
dc.contributor.author	Thompson, Madalynn Jade
dc.contributor.committeemember	Greenway, Steven C.
dc.contributor.committeemember	Krawetz, Roman J.
dc.contributor.committeemember	Ungrin, Mark D.
dc.date	2020-11
dc.date.accessioned	2020-09-03T20:35:50Z
dc.date.available	2020-09-03T20:35:50Z
dc.date.issued	2020-08-31
dc.description.abstract	The need for precision medicine has been established and the use of organoids to test individual drug efficacy and develop individual disease models is creating an opportunity for innovation. Human embryonic stem cells (hESCs) are commonly used for these applications but differentiation often results in immature phenotypes that may not be physiologically relevant. While hESCs can be differentiated into any cell type using small molecules, emerging concepts suggest that additional exogenous factors influence differentiation. In situ, stem cells exist in an organ-specific niche which contains extracellular matrix (ECM) proteins that have important paracrine effects to promote the maturity. This project aimed to investigate whether either of two alternative preparations of organ-specific ECM matrices support would offer improved support for tissue-specific differentiation and maturation. ECM matrices from porcine hearts (i.e. cardiogel) were prepared and decellularized either completely or partially. These cardiogel preparations were then studied using mass spectrometry and cytochemical staining before being used to support the maturation of hESCs that had been differentiated into cardiomyocytes (CMs). Moderate decellularization of porcine heart was achieved as shown by histochemical staining and the cardiogels contained variable amounts of important ECM components. However, neither cardiogel preparations appeared to increase the maturity of hESC-derived CMs, as assessed by cellular gene expression after 4 days of culture on cardiogel following differentiation. In conclusion, a protocol to generate cardiogels from porcine heart was achieved but significant batch variability was found. Further optimization may lead to a substrate which promotes cellular maturation and which can be used in conjunction with other technologies to increase cellular yield and homogeneity of resulting cardiac lineages.	en_US
dc.identifier.citation	Thompson, M. J. (2020). Cardiac extracellular matrix gel for ESC-derived cardiomyocyte maturation (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/38163
dc.identifier.uri	http://hdl.handle.net/1880/112491
dc.language.iso	eng	en_US
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject	Stem cell	en_US
dc.subject	Decellularization	en_US
dc.subject	Maturation	en_US
dc.subject	Differentiation	en_US
dc.subject.classification	Biology--Cell	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.classification	Biochemistry	en_US
dc.subject.classification	Engineering--Biomedical	en_US
dc.title	Cardiac extracellular matrix gel for ESC-derived cardiomyocyte maturation	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Medicine – Biochemistry and Molecular Biology	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	true	en_US