Introduction Guide to Biotechnology - Biomolecular Engineering Lab

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tal advantages of biological control for many decades,
manufacturing biological control products in marketable
amounts has been impossible. Insect cell culture removes
these manufacturing constraints. In addition, like plant cell
culture, insect cell culture is being investigated as a production
method of therapeutic proteins. Insect cell culture
is also being investigated for the production of VLP (viruslike
particle) vaccines against infectious diseases such as
SARS and influenza, which could lower costs and eliminate
the safety concerns associated with the traditional eggbased
process. A patient specific cancer vaccine that utilizes
insect cell culture has reached Phase III clinical trials.
Mammalian Cell Culture
Livestock breeding has used mammalian cell culture as
an essential tool for decades. Eggs and sperm, taken from
genetically superior bulls and cows, are united in the lab,
and the resulting embryos are grown in culture before being
implanted in surrogate cows. A similar form of mammalian
cell culture has also been an essential component
of the human in vitro fertilization process.
Our use of mammalian cell culture now extends well
beyond the brief maintenance of cells in culture for
reproductive purposes. Mammalian cell culture can
supplement—and may one day replace—animal testing
to assess the safety and efficacy of medicines. Like plant
cell culture and insect cell culture, we are relying on the
manufacturing capacity of mammalian cells to synthesize
therapeutic compounds, in particular, certain mammalian
proteins too complex to be manufactured by genetically
modified microorganisms. For example, monoclonal antibodies
are produced through mammalian cell culture.
Scientists are also investigating the use of mammalian
cell culture as a production technology for vaccines. In
2005, the Department of Health and Human Services
awarded a $97 million contract to Sanofi Pasteur to
develop mammalian cell culturing techniques to speed
the production process for new influenza vaccines and
thereby enhance pandemic preparedness.
Therapies based on cultured adult stem cells, which are
found in certain tissues like the bone marrow and brain,
are on the horizon as well. Researchers have found that
adult stem cells can be used by the body to replenish
tissues. Adult hematopoietic stem cells already are being
transplanted into bone marrow to stimulate the generation
of the various types of blood cells necessary to
rejuvenate an immune system. These stem cells can be
harvested in large quantities from umbilical cord blood,
but they are difficult to isolate and purify.
Biotechnology Industry Organization n Guide to Biotechnology
Researchers also are working on ways to harvest stem
cells from placentas and from fat. Some are looking at
cellular reprogramming as a way to get specialized body
cells, like skin cells, to revert to a primordial state so that
they can be coaxed into various types of tissues.
Embryonic stem cells are also under study as potential
therapies. As the name suggests, embryonic stem cells are
derived from embryos—specifically those that develop from
eggs that have been fertilized in vitro (in an in vitro fertilization
clinic) and then donated by consent for research purposes.
The embryos are typically four or five days old and are
each a hollow microscopic ball of cells called the blastocyst.
The potential value of stem cell therapy and tissue
engineering can best be realized if the therapeutic
stem cells and the tissues derived from them are
genetically identical to the patient receiving them.
Human embryonic stem cells are isolated by transferring
the inner cell mass into a nutrient rich culture medium.
There the human stem cells proliferate. Over the course
of several days, the cells of the inner cell mass divide and
spread all over the dish. Researchers then must remove
the growing cells and divide them into fresh culture
dishes. This process of replating the cells, called subculturing,
is repeated many times over many months. Each
cycle of subculturing cells is called a passage. Embryonic
stem cells that have proliferated in cell culture for six or
more months without differentiating (i.e., remain pluripotent)
and appear genetically normal are referred to as
an embryonic stem cell line.
The inner surface of the culture dish may be coated with
mouse embryonic skin cells that have been engineered
not to divide. This is called the “feeder layer.” It provides a
sticky surface to which the human embryonic cells attach.
Recently scientists have been figuring out ways to grow
embryonic stem cells without using mouse feeder cells—a
significant advance because of the risk of viruses and
other macromolecules in the mouse cells being transmitted
to the human cells.
The potential value of stem cell therapy and tissue engineering
can best be realized if the therapeutic stem cells
and the tissues derived from them are genetically identical
to the patient receiving them. Therefore, unless the patient
is the source of the stem cells, the stem cells need to be
“customized” by replacing the stem cell’s genetic material
with the patient’s before cueing the stem cells to differentiate
into a specific cell type. To date, this genetic material
replacement and reprogramming can be done effectively
only with embryonic stem cells.