A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays

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Title: A defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarrays
Author(s): Patel, AK
Celiz, AD
Rajamohan, D
Anderson, DG
Langer, R
Davies, MC
Alexander, MR
Denning, C
Item Type: Journal Article
Abstract: Cardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 μM in cardiomyocytes cultured on the co-polymer compared to 0.5 μM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.
Publication Date: 15-May-2015
Date of Acceptance: 14-May-2015
URI: http://hdl.handle.net/10044/1/52126
DOI: https://dx.doi.org/10.1016/j.biomaterials.2015.05.019
ISSN: 0142-9612
Publisher: Elsevier
Start Page: 257
End Page: 265
Journal / Book Title: Biomaterials
Volume: 61
Copyright Statement: © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
Stem cell
Cardiomyocyte
Cell adhesion
Cell spreading
Electrophysiology
Surface analysis
SURFACE
DIFFERENTIATION
DOXORUBICIN
MATURATION
GROWTH
ADSORPTION
ATTACHMENT
POLYMERS
ADHESION
PROTEIN
Cardiomyocyte
Cell adhesion
Cell spreading
Electrophysiology
Stem cell
Surface analysis
Batch Cell Culture Techniques
Biocompatible Materials
Cell Adhesion
Cell Differentiation
Cell Line
Cell Movement
Cell Proliferation
Combinatorial Chemistry Techniques
Culture Media, Serum-Free
Humans
Materials Testing
Myocytes, Cardiac
Polymers
Stem Cells
Cell Line
Myocytes, Cardiac
Stem Cells
Humans
Polymers
Biocompatible Materials
Culture Media, Serum-Free
Combinatorial Chemistry Techniques
Materials Testing
Cell Adhesion
Cell Differentiation
Cell Proliferation
Cell Movement
Batch Cell Culture Techniques
Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
Stem cell
Cardiomyocyte
Cell adhesion
Cell spreading
Electrophysiology
Surface analysis
SURFACE
DIFFERENTIATION
DOXORUBICIN
MATURATION
GROWTH
ADSORPTION
ATTACHMENT
POLYMERS
ADHESION
PROTEIN
MD Multidisciplinary
Biomedical Engineering
Publication Status: Published
Appears in Collections:Faculty of Engineering
Bioengineering



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