Artificial Support and Replacement of Human Organs - Biomimetics: Biologically Inspired Technologies - page 452

Although hemodialysis revolutionized the treatment of kidney failure, it is far from perfect in
mimicking the functions of the kidney. Patients need to be hooked to the machine for prolonged
periods and therefore limit their mobility. Besides removing the toxic waste and maintaining the
electrolyte and water balance, the human kidney plays an important role in terms of endocrine and
metabolic activities. To solve this problem, and mimic the functioning of a normal human kidney,
developments are underway to develop a bio-artificial kidney which incorporates tubular cells in
the hollow fibers (Moussy, 2000). Cells are grown as confluent monolayers along the inner surface
of these hollow fibers; the membrane acts as a scaffold and allows the cells to carry out the
important metabolic and endocrine activities (Humes et al., 1997; Nikolovski et al., 1999). Another
novel aspect of these cell-seeded hollow fibers is that the cells are not exposed to the patient's blood
and hence do not develop an immune response (Humes et al., 1997). Early results of these systems
are encouraging.

18.4 ARTIFICIAL LIVER

The liver plays an important role in the detoxification, synthesis, and digestion in the body.
Currently, liver transplantation is the only viable and satisfactory option for liver failure (UNOS,
2003; van de Kerkhove et al., 2004). But the paucity and mismatch of demand and supply
of available donors is a major impediment for widespread application of this therapy. The liver
has a tremendous capacity to regenerate and if given adequate time to rest, the liver has the
capability of regrowing the damaged cells and can potentially recover. Currently, support systems
function as a bridge and try to exploit this regenerative capacity of the damaged liver until recovery
or transplantation. Attempts to replace the function of the liver are complex and currently are in
their infancy. Several earlier attempts to use hemodialysis to remove undesirable toxic products did
not meet with success (van de Kerkhove et al., 2004). Several other modalities like hemofiltration,
hemodiafiltration, and hemodiabsorption were not particularly attractive (van de Kerkhove et al.,
2004). One of the reasons is that these systems replace only one or two of the myriad functions
undertaken by the liver. However, a few of the promising techniques include the Molecular
Adsorbents Recirculating System (MARS), Artificial Liver Support Systems, and Albumin Dialysis
System (Jalan et al., 2004; Mullin et al., 2004; van de Kerkhove et al., 2004). These are based on
detoxification of water soluble and protein bound toxins in dialysis (Boyle et al., 2004). But all of
these systems share the common disadvantage of inability to synthesize and produce liver specific
factors and proteins.
The above limitations have turned attention to options of biologically mimicking organ function
by using liver cells from animal and human origin (Kobayashi et al., 2003; Liu et al., 2004a-c).
Theoretically, they can carry out detoxification, metabolic function, and synthesize important
proteins. Earlier attempts involved using cross-circulation with animal livers or liver-tissue pre-
parations (van de Kerkhove et al., 2004). Liver cells can be used in suspended, attached, or
encapsulated fashion with the aid of a semipermeable membrane akin to a bio-artificial kidney.
These are collectively called bio-artificial liver systems (Demetriou et al., 2004; Fruhauf et al.,
2004; Kobayashi et al., 2003; Liu et al., 2004a-c). Currently, there are few systems available which
have undergone even limited human trials (Demetriou et al., 2004). They include the Extracorpor-
eal Liver Assist System (ELAD), which uses a transformed hepatocyte cell line (Figure 18.1). Other
systems such as the HepatAssist System, the TECA-hybrid artificial liver support system, the bio-
artificial liver support system, the radial flow bioreactor, the liver support system, the AMC-
bio-artificial liver, and the bio-artificial hepatic support system, all use porcine derived hepatocyte
cells (Demetriou et al., 2004; van de Kerkhove et al., 2004). However, there are concerns about
using tumor derived or transformed cells due to their potential to develop cancer. On the other hand,
porcine cells pose the risk of exposing the human body to animal tissue thus setting up an immune
response and the added risk of transporting infections from animals to humans. The widespread