Tissue Engineering and Liver Regeneration: An Overview

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06 Feb 2019
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Introduction
Tissue engineering is defined as the reconstruction of cells into the differential cell of the
desired organ or tissue, with an intention to improve the functioning of that organ (Lanza,
2011). This involves the combination of cells, engineering materials, factors suitable for
biochemical and physiological conditioning. Regenerative medicine is a part of the tissue
engineering which uses the bio-engineering principle for treatment (Atala, 2018). To solve
the health related issues, it uses innovative methods, ideas and synthesizes various
biomaterials constructs (Ratner, 2013).
Cell and tissue structure and function
Liver is the largest gland present in human body that comprises of mainly hepatic cells (60%
of tissue). Other cell line include kupffer cells, and vascular system. It secretes bile, digestive
fluids, stores glycogen, metabolizes fat, protein, and carbohydrate, and synthesize blood
clotting factors. The hepatocytes present in liver consists of high regenerative capacity which
makes the liver one of the regenerative organ. However, when these hepatocytes are
maintained in vitro they tend to deteriorate faster functionally (Vildhede, 2018).
Tissue dynamics
Liver secretes more than 900 ml of bile every day, which is required for digestion.
Additionally, it is also involved in secretion of enzymes, blood-clotting factors and is
involved in storage. The cells proliferated with the help of matrix based transplantation
system leads to dysfunction and loss of cells. This might be caused because of the change in
nutrients and the absence of blood flow, which is important to be considered while focusing
on liver tissue engineering.
Natural rate of renewal/maintenance
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Liver tissue have the maximum capacity of regeneration in human body system, which is
commonly known as pluripotency (Arumugaswami, 2016). Despite its inherent tendency of
regeneration in vivo, the hepatocytes proliferate weakly in vitro. This eventually makes the
culturing process and effort more difficult for the researcher. The functional characteristics of
the cell line demands immediate access to the vascular pool in the search of nutrient and
removal of metabolic waste. This in turn creates an obstruction on the engineering histio-
substitutive constructs (Burra, 2016, pp.433).
Wound healing/regenerative processes
Tissue engineering of liver uses biologically compatible scaffolds that facilitates smooth
conditions for the growth. This form engineering is primarily concerned with i) designing of
external device for liver support, ii) in vivo liver regeneration with the help of cell
transplantation, and iii) implantable devices (Mazza, 2018, pp.131).
Cells
Phenotypes (identification)
Human hepatocytes are recognized cell source to be used in implantable devices and BAL.
Due to isolation from the discarded cadaveric liver samples, there exists only limited primary
human hepatocytes.
Sources
For the purpose of liver tissue engineering adult, induced and embryonic important stem cells
are being used. The primary benefit of using stem cells is its proliferation characteristics that
makes is possible to grow scalable amount of cells (Sakiyama, 2017, p.1974). Apart from
this, the stem cells are adept of expanding into any cell type within human body. This feature
of stem cell represents an inexhaustible source of cell. The various types of stem cells used in
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liver regeneration includes adult stem cells, Oval cells, induced and embryonic pluripotent
stem cells, hepatoblast, hepatocyte-like cells, and human foetal hepatocytes.
In-vitro culture, bioreactors, cell and gene therapy, immune rejection
In this section, it is important to discuss about porcine hepatocytes, which is considered as
one of the most efficient and cheap source of cell for liver tissue engineering. Due to limited
availability of human hepatocytes, the cells of pig are used (because of similar physiology) in
implantable devices and BAL. Several of efforts are being made to maintain functional
performance of hepatocytes through extra cellular matrix (ECM) (Swinehart, 2016, pp.351).
However, there is risk of transfer of the protein related incompatibility, zoonotic diseases, and
immune responses (Morini, 2018, pp.301).
ECM
Composition/identification & Man-made substitutes
Various materials (including natural components, biomaterials, and nano-materials) used in
the tissue engineered scaffolds includes the followings, as discussed below:
 Poly-Terephthalate (PET) film - The 3-D culture on the film was started for surface
modification like of ECM proteins coated on collagen, fibro-nectin, and gelatine.
These strategies are helpful for BAL-based devices and drug screening platforms
(Saldin, 2017, pp.1).
 Matrigel - When the non-transformed cell line of human hepatocyte is cultured on the
3D matrigel, which then forms structure similar to tissue, from the cells which further
reacquire the liver specific functions.
 Hydrogels – These are the injectable scaffolds used for the purpose of cell
transplantation for their proliferation and biodegradability. This technique is
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