Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts
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Cheng-2009-Insulin-like Growth.pdf
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Author(s)
Cheng, Mingyu
Moretti, Matteo
Engelmayr, George C.
Freed, Lisa E.
Date Issued
August 2008
Journal
Tissue Engineering. Part A
Publisher
Mary Ann Liebert, Inc.
Citation
Cheng, Mingyu et al. “Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts.” Tissue Engineering Part A 15.3 (2009): 645-653. ©2009 Mary Ann Liebert, Inc.
Version
Final published version
Abstract
Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p < 0.01), cellular viability (p < 0.01), contractile amplitude (p < 0.01), and excitation threshold (p < 0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p < 0.01), connexin-43 (p < 0.05), and total protein (p < 0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p < 0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1089/ten.tea.2008.0077
