Biomedical Engineering Reference
In-Depth Information
engineering,” which is a novel tissue engineering methodology,
can make possible the fabrication of three-dimensional (3D)
and functional tissues without any artificial scaffolds by using a
temperature-responsive culture dish [56-64]. In various animal
models, bioengineered 3D tissues using autologous cells can be
transplanted into various tissues, including heart tissue, without
cell loss, and the transplantation into damaged heart can give higher
enormous therapeutic effects than dissociated cell injection via the
production of several growth factors, which show paracrine effects,
such as (1) angiogenesis, (2) antifibrosis, (3) antiapoptosis, and (4)
stem cell recruiting. Clinical trials for curing heart disease using
these tissue engineering methodologies have already performed
[65-67].
For further advanced regenerative therapy, attempts to engineer
pulsatile myocardial tissue have been already started. In the native
myocardium, electrical coupling between cardiomyocytes occurs via
gap junctions (GJs), which mediate the exchange of small molecules
and ions between neighboring cells and are critical to a synchronized
and functional beating [1]. Therefore, electrical couplings between
cardiomyocytes via functional GJ formation are essential for the
reconstruction of functional myocardium. Tissue engineering
methodology allows us to fabricate electrical communicative
myocardial tissues, which pulse spontaneously, synchronously,
and macroscopically [49, 57]. The transplantation of pulsatile
bioengineered myocardial tissue is expected to assist directly in
the mechanical pumping ability of damaged heart; therefore, the
bioengineered tissue can give not only a paracrine effect but also
a mechanical effect to the damaged heart, resulting in more strong
therapeutic effects than that of nonpulsatile tissue, which can give
only a paracrine effect. In fact, after being transplanted in animal
models, bioengineered 3D cardiac tissue shows functional and
electrical couplings with the host myocardium [50, 61]. For the
realization of a bioengineered organ, some groups have challenged
the fabrication of vascularized thicker myocardium and engineered
tissues with a pumping function [68-72]. As a clinical available
pulsatile cardiomyocyte source, human embryonic stem cells
(ESCs) [73] and induced pluripotent stem cells (iPSCs) [74, 75]
have attractive potentials because the stem cells can efficiently
differentiate into beating cardiomyocytes [76-78]. Furthermore,
several methods to enrich differentiated cardiomyocytes with a
