Naturally occurring extracellular matrix (ECM) has been shown to promote
constructive remodelling as opposed to scar tissue formation in a variety of body systems,
including but not limited to the lower urinary tract, esophagus, myocardium, arteries and
veins, tendons and ligaments. Most studies have used ECM that was not chemically
crosslinked or otherwise altered by processing and that was isolated from porcine small
intestinal submucosa or urinary bladder matrix (UBM). The single or multilayered sheet
forms of these materials have practical limitations with regard to their shape, threedimensional form, and clinical utility. A particulate form of ECM is of interest for
injection into tissues and for the development of 3D scaffolds (Clarke et al., 2014).
When we get whole heart with end-stage disease we need to remove all cellular
and nuclear material while minimizing any adverse effect on the composition, biological
activity, and mechanical integrity of the remaining ECM by using decellulerization
technique (Song et al., 2012). The most robust and effective decellularization protocols
include a combination of physical, chemical, and enzymatic approaches. A
decellularization protocol generally begins with lysis of the cell membrane using physical
treatments or ionic solutions, followed by separation of cellular components from the
ECM using enzymatic treatments, solubilization of cytoplasmic and nuclear cellular
components using detergents, and finally removal of cellular debris from the tissue. These
steps can be coupled with mechanical agitation to increase their effectiveness. Following
decellularization, all residual chemicals must be removed to avoid an adverse host tissue
response to the chemical (Gilbert et al., 2013).
After we get a heart scaffold contain ECM from decellularization technique, all we
need to do is fill it with stem cells that will grow and fill the scaffold. The latest
breakthrough for human heart construction is using induced pluripotent stem cells (iPSCs)
for recellulerization. Compared with CMs directly isolated from patients under heart
transplantation with end-stage heart diseases, human iPSC-derived CMs are renewable
and free of prolonged pharmaceutical treatment. Thus, human iPSCs and the
decellularized whole-heart ECMs (DC-ECMs) theoretically provide a novel platform for
making personalized heart tissues. A previous study reported the repopulation of
decellularized hearts using human undifferentiated embryonic stem (ES) cells. However,
contractility and electrical activity were not detected in those engineered heart tissues
(Guethoff et al., 2013). The newest report of engineered human heart by repopulating
whole decellulerized mouse heart with human iPS cell-derived multipotential
cardiovascular progenitors (MCPs) (Heidenrich et al.,2013).
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