Page 140 - IJB-10-3

International Journal of Bioprinting New challenges in liver tissue engineering

Table 3. (Continued...)
Partial hepatectomy
Decellularized rat Primary rat Lewis rats with – Improved survival and functionality.
liver coated with hepatocytes hepatectomy (90%) – Absence of thrombosis. 169
heparin
– Active blood flow through the graft.
Decellularized pig Pig hepatocytes + Pigs with – Preservation of the architecture of the transplanted graft. 156
liver endothelial cells hepatectomy (60%) – Reduction of injury markers (bilirubin, transaminases,
inflammation markers).
– Human MSCs were differentiated within scaffolds and then
Hydrolyzed tetra- Human Wistar rats with transplanted.
ethylorthosilicate, mesenchymal partial hepatectomy – After transplantation, cells storage glycogen and showed the 157
chitosan, Alg, Col stem cells (70%) expression of hepatic markers (AFP, CK19, CK18, albumin, HNF-
I scaffolds
3b, and MRP-2).
– Increased survival (80% vs. 50%, transplanted vs. control).
Bone marrow Sprague–Dawley
Alg scaffolds mesenchymal rats with partial – Improved liver function (reduced transaminase levels). 158
– MSCs on Alg scaffolds secreted albumin and produced glycogen 4
stem cells hepatectomy (70%)
weeks after transplantation.
Polyacrylonitrile Pig hepatocytes – Increased survival of transplanted animals.
sodium meth- (fresh and Lewis rats + – Fresh or cryopreserved hepatocytes preserved their ultrastructure. 170
ylallylsulfonate cryopreserved) hepatectomy (95%) – Partial maintenance of CYP3A4 activity in transplanted constructs.
hydrogels
Fibrosis/Cirrhosis
– Implanted cells survived and hosted the native tissue.
Rat neonatal and Sprague–Dawley rat – Cells had characteristic hepatocyte morphology.
Col I hydrogels 163
adult hepatocytes + cirrhosis (CCl ) – Reduction of fibrosis after multi-site injection of collagen hydrogels
4
containing hepatocytes.
– Increased survival in treated animals.
Rat liver cells + Wistar rat + CCl - – Reduction of transaminases levels in transplanted animals.
Col hydrogel 4 164
MSCs induced fibrosis – Reduction of the fibrotic areas assessed by histology.
– Reconstruction of transplanted tissue after 90 days.
Other models
– Complete decellularization of whole human liver.
– dECM human liver scaffolds were successfully repopulated with
Decellularized Sk-Hep-1, HepG2, Immunocompetent different human liver cell types. 148
human liver cubes and LX2 mice
– Interspecies biocompatibility was demonstrated by transplanting
dECM cubes into immunocompetent mice.
Abbreviations: ALF, acute liver failure; Alg, alginate; ALT, alanine transaminase; AST, aspartate transaminase; Col, collagen; dECM, decellularized
extracellular matrix; EpCAM, epithelial cell adhesion molecule; Gel, gelatin; HA, hyaluronic acid; HGF, hepatocyte growth factor; HLC, hepatocyte-like
cells; MSC, mesenchymal stem cells; PHH, primary human hepatocytes.

developed systems for disease modeling. Secondly, many 3D configuration has been described as an optimal method
studies focus on maintaining the hepatocyte phenotype that could better recapitulate liver physiology, the random
without considering the liver’s multicellularity. In fact, distribution of the cells, their limited expansion capability,
Takebe et al. attempted to recapitulate early organogenesis and the problems associated with maintaining functionality
by creating liver buds that contain hepatic endoderm cells for longer periods remain as important challenges to be
from iPSCs, HUVECs, and MSCs and demonstrated their addressed. Finally, most of the animal models used in
171
increased functionality in vitro, along with their ability the regenerative medicine approach are based on the use
to rescue an animal model of drug-induced lethal failure of partial hepatectomy or ALF; thus, more animal models
and achieve human vascularization. The development that reflect other aspects of liver disease should be used to
83
of an angiogenic response for regenerative medicine determine the efficacy of the developed systems.
applications would thus be essential to achieve long-term
effects. On the other hand, despite the fact that the co- On the other hand, future studies will be directed to
culture of hepatocytes and other non-parenchymal cells in searching for biomaterials with the appropriate mechanical

Volume 10 Issue 3 (2024) 132 doi: 10.36922/ijb.2706