44
Bioprocess Engineering
animals to produce proteins. The primary
concern is safety. Besides the possibility
of having a negative health effect on the
animal, there is fear regarding mutation
of animal viruses that jump species and
become a serious health issue for humans.
The fear is real since some viruses such
as AIDS and SARS that still lack effective
treatment are believed to have originated in
animals. Screening of animals for viruses
is an extremely expensive undertaking and
may limit the cost effectiveness of their
use for production.
Transgenic plant technology holds great
promise and products are currently in
Phase I clinical trials. Large companies
including Monsanto, Dow Chemical, and
Sigma-Aldrich are teaming with smaller
companies such as Prodigen, Inc. and
Epicyte Pharmaceutical to manufacture
antibodies and proteins in transgenic
plants. Several crops including corn, to-
bacco, potatoes, and soybeans have been
studied for production of antibodies and
proteins. Products tend to degrade within
the tobacco leaf and potato; protein sep-
aration from soybeans is more challeng-
ing; but corn results are very promising.
The product, especially antibodies, con-
centrates in the corn kernels, and is easily
separated. The demand is for ‘‘green’’
engineering processes. The desire is to
eliminate environmental hazardous waste
generation altogether. Thus, a green plant
that works as a bioreactor is an extremely
attractive, environmentally friendly alter-
native. The systems are also safe in terms
of virus transmission, since plant viruses
do not survive in animals. One concern
is the ability to keep the plants isolated
from other crops. The pharm plant prod-
ucts, as they are being called, cannot be
allowed into the food chain. So currently
these plants are not grown in any food pro-
ducing areas. The tremendous advantage
of using pharm plants to make antibodies
and other products is that the estimated
production costs are an order of magni-
tude less than the cost of production using
mammalian cells. This savings will push
the development of transgenic plant prod-
ucts forward.
5
Transport and Adhesion of Cells
Cellular and viral transport and adhesion
are important in immobilized reactors,
the development of new drugs, tissue
repair, drug delivery,
in situ
bioremedi-
ation efforts, and security issues related
to bioterrorism. Understanding how cells
are able to recognize and adhere speciF-
cally to insoluble extracellular tissue matrix
proteins and to other cells is crucial to
many physiological processes. Cells of all
types – blood, bacterial, tumor, and en-
dothelial – respond to environmental stim-
uli through receptors found on their cells
surfaces. ±or example, a cell will have a re-
ceptor on its surface for epidermal growth
factor; binding and internalization of the
growth factor then stimulates DNA synthe-
sis. Cell receptors are responsible for cell
adhesion to surfaces such as tissue, scaf-
fold reactors, and for self-agglutination.
White blood cells adhere to ligands on
vessel walls, or mammalian cells adhere
to surfaces coated with ligands through
integrins. Cell receptors are also respon-
sible for chemotaxis – the migration of
cells in response to a speciFc chemical
gradient. Chemotaxis is of particular im-
portance in the development and repair of
inflammations.
Understanding
the
mechanisms
of
intra- and intercellular transport is the
key to the development of site-directed
or target-speciFc drugs. ±or instance,
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