Biomedical Engineering Reference
In-Depth Information
12.7
Photographs of patients who received cultured skin substitutes
(CSS) and autograft (AG). Left:
After 7 years in an African-American,
healed skin from CSS remains pliable, and low in scar formation,
except for obvious hypopigmentation with foci of pigment (arrows).
Right: At 2 years in this Hispanic patient, CSS also remains
hypopigmented. Individual foci of pigment are interpreted as melano-
cyte populations arising from single melanocytes in CSS. Scales in cm.
12.7.4 Stem cell and gene therapy
Using the tools of molecular biology, genetic modification of cells within skin
substitutes can hypothetically be used to overcome limitations in anatomy and
physiology resulting in skin substitutes with greater homology to native human
skin and improved performance. The gene expression profile of keratinocytes can
be altered by the transfer of recombinant genes
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and these genetically modified
cells have been shown to retain their ability to differentiate into a stratified
epidermis.
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Genetic modification can be used ectopically to express cytokines
not normally expressed in a particular cell type and to compensate for deficiencies
of engineered skin. Alternatively, skin substitutes can be genetically engineered to
overexpress growth factors that aid in wound healing to enhance their therapeutic
value for wound repair. For example, cultured skin substitutes comprised of
keratinocytes genetically modified to overexpress vascular endothelial growth
factor, a mitogen for endothelial cells, show enhanced vascularization and im-
proved healing on mice compared to non-modified CSS.
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Genetically modified
CSS can also serve as a vehicle for cutaneous gene therapy which could possibly
correct genetic diseases such as epidermolysis bullosa (EB). Junctional epidermo-
lysis bullosa (JEB), a severe form of the disease, can result from mutation of genes
encoding subunits of laminin-5, a component of anchoring filaments in the
