Engineered cardiac model systems for dilated cardiomyopathy
Citation for published version (APA):
Spreeuwel, van, A. C. C., Bax, N. A. M., Schaft, van der, D. W. J., & Bouten, C. V. C. (2011). Engineered cardiac
model systems for dilated cardiomyopathy. Poster session presented at Mate Poster Award 2011 : 16th Annual
Poster Contest.
Document status and date:
Published: 01/01/2011
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Accepted manuscript including changes made at the peer-review stage
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Engineered cardiac model systems
for dilated cardiomyopathy
A.C.C van Spreeuwel, N.A.M. Bax, D.W.J van der Schaft, C.V.C Bouten
Introduction
Dilated
cardiomyopathy
(DCM)
is
characterized
by
diminished
contractile
function
and
progressive
enlargement of the heart. It is the leading cause of heart
failure and DCM patients suffer from arrhythmia and risk a
sudden death
[1]. The goal of this project is to develop an
engineered cardiac model
Tissue stiffness will be determined using indentation tests
(fig. 2), which can be related to the matrix composition, as
determined by histology (fig. 3). Furthermore, tissue
composition in both healthy and diseased myocardium will
be studied by performing immunohistochemistry.
system of healthy and
Fig 1. Project overview: To create an engineered cardiac model system, we will characterize the native environment of cardiomyocytes in healthy and diseased tissue. Furthermore HL-1 murine cardiomyocytes will be used as healthy cells, and they can be transfected or treated with drugs to induce ‘disease’.
Native Tissue properties
The composition, architecture and mechanical properties
Figure 3: Masson’s Trichrome staining on healthy (A) and diseased (B) mouse myocardium with cells in red and collagen in blue. Diseased tissue had more collagen an a more chaotic structure compared to healthy tissue.
Healthy and diseased cells
The HL-1 murine cardiomyocyte cell line, will be used to
develop our engineered cardiac model system. Since this
cell line has been studied in 2D only
[2,3], we will start by
investigating the application for making 3D constructs
(fig.4).
system of healthy and
dilated cardiac tissue to
perform studies on the
effect
of
DCM
on
mechanical
properties
resulting from changes in
cell-cell
and
cell-matrix
interactions.
Native tissue properties Healthy and diseased cells Engineered cardiac model systemA
B
/ Soft Tissue Biomechanics and Engineering
The composition, architecture and mechanical properties
of healthy and diseased cardiac tissue from mouse
models, as well as from human cardiac biopsies, will be
determined to mimic the native environment of cardiac
cells in engineered cardiac models system.
Figure 2: Results of initial indentation tests on porcine myocardium.
Figure 4: HL-1 cells in 2D (A) and in a 3D hydrogel (B) stained for actin in red and nuclei in blue. HL-1 cells in 2D have a more spread morphology and more stress fibers, compared to 3D, where the cells have a more round morphology.
Future Research
Different mouse models for DCM will be characterized by
immunohistochemistry and indentation tests to provide
input for the engineered cardiac model system. The HL-1
cardiomyocytes will be used make 3D cardiac tissue
models to perform studies on the effect of DCM on cell-cell
and cell-matrix interactions.
A
B
[1] Taylor et al. Orphanet.J.Rare.Dis. 2006. [2] Claycomb et al. Proc.Natl.Acad.Sci. 1998. [3] White et al. Am.J.Physiol.Heart.Circ. Physiol, 2004
