Biomedical Engineering Reference
In-Depth Information
they are capable of differentiating into both hepatocytes and bile
duct epithelial cells.
69
The bone marrow contains stem cells capable of migrating
throughout the body and differentiating into various cell types,
includinglivercells.
63
AlmostalllivercelltypessuchasKupffercells
andepithelialcellsliningthebileductsmayoriginatefromthebone
marrow. In the bone marrow, there are certain populations of stem
cell sources such as hematopoietic stem cells, marrow stromal stem
cells, and multipotent adult progenitor cells.
Fetal hepatocytes are highly proliferative, which may facilitate
engraftment and expansion of transplanted cell population.
70
The
transplantation of fetal rat liver cells in hepatectomized rats results
intheformationof500-1,000cellclusterswithintwotosixmonths,
showing 9 or 10 cell divisions, whereas adult hepatocytes trans-
planted under similar conditions undergo only 1 or 2 cell divisions,
although ethical concerns need to beaddressed.
71
The establishment of an immortal hepatocyte cell line that can
be continuously grown in unlimited quantities while retaining dif-
ferentiated hepatocytes is highly desirable because present cell cul-
ture conditions have not allowed extensive proliferation of primary
hepatocytes.
72
A number of proliferating human cell lines were
immortalized by virtue of cultural conditions without the use of
oncogenes or carcinogens, although considerable limitations inhibit
their clinical utility due to the metabolic activity.
73
Also, cell immor-
talization can be generated by transferring specific oncogenes into
these hepatocytes. Among them, the simian virus (SV)40T antigen
was used for enhancing proliferation in hepatocytes.
74
Kobayashi
et al
.
75
used a reversible immortalization system with the SV40T
antigen and Cre-Lox recombination targeting human hepatocytes in
their final differentiated state.
Genetically engineered hepatocytes can already correct specific
congential enzyme deficiencies;
ex vivo
gene therapy to correct
human familial hypercholesterolemia using a retroviral vector has
met with success.
76
An
ex vivo
approach to gene therapy for familial
hypercholesterolemia (FH) has been developed in which the recipi-
ent is transplanted with autologous hepatocytes that are genetically
corrected with recombinant retroviruses carrying the low-density
lipoprotein (LDL) receptor.
77
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