Assessment of Combined Matrix and Bioelectric Signaling on Cardiac Progenitor Cell Differentiation
Daley, Mark.
2020
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Thesis (M.S.)--Tufts
University, 2020.
Submitted to the Dept. of Biomedical Engineering.
Advisor: Lauren Black.
Committee: Madeleine Oudin, and Michael Levin.
Keyword: Biomedical engineering.
Cardiac progenitor cells from both primary and induced pluripotent stem cell culture represent a promising source of cardiovascular cells. However, the ... read morefactors that influence their differentiation are still not entirely understood. Historically, the field of tissue engineering has been adept at modulating the chemical and physical cellular microenvironment. This approach has yielded significant progress, but more is needed to integrate our understanding of other fundamental cell signaling paradigms. Bioelectric signaling has been demonstrated to be a vital part of tissue development, regeneration, and function across organ systems and the extracellular matrix is known to alter the bioelectric properties of cells. Thus, bioelectric signaling and its interaction with matrix signaling represent a promising avenue for driving differentiation of cardiac progenitor cells. Pediatric c kit+ cardiac progenitor cells were initially utilized for this purpose. Cardiovascular differentiation was assessed while resting membrane potentials altered by small molecule treatment during culture on fetal or adult extracellular matrix. Smooth muscle, but not endothelial or cardiac, differentiation was strongly modified by changes in resting membrane potential. Smooth muscle phenotype was associated with depolarization and inversely related to hyperpolarization. Endothelial and cardiac expression remained unchanged regardless of treatment. Expression of smooth muscle proteins was also modified by matrix developmental age, with fetal ECM appearing to amplify the effects of resting membrane potential. When cultured on polyacrylamide hydrogels with different elastic moduli, stiffer substrates were found to promote vasculogenesis of cardiac progenitor cells. These methods were subsequently expanded to investigate matrix-bioelectric crosstalk in induced pluripotent stem cells. Early cardiomyocyte maturation was enhanced when membrane potential was altered by small molecule treatment. Attempts to seed induced pluripotent stem cells onto matrix-coated substrates, however, resulted in spontaneous differentiation. Future investigations will need to develop alternative culture methods with which to assess cardiovascular fate specification in complex matrices. Ultimately, combining matrix composition and bioelectric signaling represents a potential alternative for guiding cardiac progenitor cell behavior in tissue engineering and regenerative medicine.read less - ID:
- z029pk55z
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