Biomedical Engineering Reference
In-Depth Information
Fig. 7.1.3-4 The bioartificial liver. Several closely related versions of this intermittent extracorporeal therapy format have undergone
preliminary clinical trials.
bioartificial pancreas, and the delivery of cell and gene
therapy. As in all areas of tissue engineering, technology is
moving rapidly and
Table 7.1.3-2
should be appreciated in
historical rather than current context.
The bioartificial liver currently is being evaluated as
a ''bridge to transplant,'' i.e., to extend the lifetime of pa-
tients who are medically eligible for liver transplantation
until a donor organ becomes available. Several designs and
treatment protocols have been proposed; one appealing
format is shown in
Fig. 7.1.3-4
. The extracorporeal circuit
is broadly similar to that used in dialysis for the treatment
of kidney failure. Blood is continuously withdrawn from
the patient's vasculature, at a rate of 200-300 ml/min,
treated in a hollow-fiber bioartificial liver, and ultimately
returned to the patient. A charcoal filter may be added to
further detoxify the blood. Treatments are performed
daily for 4 hours. Results in early human trials were quite
encouraging and several cases of recovery without trans-
plantation were observed.
The bioartificial pancreas has enjoyed very impressive
success in rodent studies
proven difficult: formats that were suitable in rodents
generally have been unsatisfactory in large animals. Some
investigators believe that use of genetically engineered
cells or their transgenic cohorts may solve the problem of
cell source. Genetically engineered cells might be more
productive than islets and ease some of the constraints on
device design. Development of a clinically beneficial
bioartificial pancreas remains an important challenge for
biomedical engineering in the early 21st century.
Encapsulation is also being developed for the delivery
of cell and gene therapy. Small quantities of cells pro-
ducing a desired therapeutic molecule are placed inside
the lumen of a sealed hollow fiber or encapsulated in
microspheres. A therapeutic dose may involve a very
manageable 1-10
10
6
cells (roughly two orders of
magnitude fewer cells than would be required for
a bioartificial pancreas). From one perspective, these
devices represent a form of drug delivery providing
point-source, time-constant, and site-specific delivery
with the added benefit of a ''regenerable'' source of bio-
active ''drug.'' In another sense, when recombinant cells
are involved, this approach can be considered a form of
gene therapy in which the transplanted gene resides in
cells housed in a capsule rather than directly in the cells
of the recipient. The technical issues involved in this
form of encapsulated cell therapy are largely resolved.
Several successful preclinical and clinical trials have been
reported.
so much so that no fewer than
five reports on ''proof of principle'' experiments have
appeared in the hallowed pages of
Science
magazine. Un-
fortunately, results from larger animal models and human
studies have been disappointing. Investigators have not
been able to reliably isolate the number of islets (500,000
to 1,000,000 or 2
10
9
cells) required for a large re-
cipient. Moreover, species scaling of device design has
d
