Biomedical Engineering Reference
In-Depth Information
The tremendous ability of epidermal SC to continuously produce large quantitiy
of human keratinocytes which undergo terminal differentiation [
29
] has made it
possible to develop skin grafts from a small skin biopsy within 2-4 weeks [
30
].
These tissue engineered products have been used successfully in the treatment of
chronic skin wounds and burns. While autologous skin grafting, consisting in the
use of a piece of skin removed from the same patient and transplanted to the
wound area, is the treatment of choice for limited skin injuries, it cannot be
employed in extensive burns. In such cases, only few cells SC removed from the
unaffected skin can be cultured and produce sufficient keratinocytes to cover in an
autologous manner the entire skin surface, being thus lifesaving for the most
severely burned patients. Considering that the number and size of HF have an
impact on the number of SC present in the corresponding culture, it has been
shown recently that biopsies taken from the periauricular skin allow a easier HF
extraction and yield the highest number of SC [
31
]. All in all, few SC derived from
a tiny piece of proper skin, possibly rich in HF, allows the regeneration of large
sheets of skin that can successfully treat extensive wounds with good esthetical
results.
4.4 Genetic Skin Diseases
There are a number of devastating genodermatoses that do not respond to any
conventional cure. For monogenic diseases, gene therapy has the capability to
ameliorate them and potentially be a decisive treatment. SC are the best choice for
gene therapy because of their ability to self-renew indefinitely and their potential
to produce differentiated cells. Adult skin is easy to access, allowing the recovery
of a high number of SC that can be expanded in culture, genetically modified and
transplanted into the diseased skin, where they allow the transgene to remain stable
for a long time [
32
,
33
]. Among genetic skin diseases, the family of epidermolysis
bullosa (EB) includes severe conditions characterized by the disruption of dermal-
epidermal junction. EB is classified into simplex, junctional, and dystrophic
according to the site of defect of genetic defect. Junctional EB is caused by an
autosomal recessive mutation in one chain of laminin-5, an essential component of
the hemidesmosome. Laminin deficiency leads to various degree of severity, from
early mortality (Herliz variant) to disfiguring and painful blisters, recurrent
infections, and skin cancer [
34
]. Mavilio and co-workers were able to fix laminin-5
deficiency in junctional EB through transplantation of cultured skin derived from
genetically modified epidermal SC, thus achieving a full functional protein and the
amelioration of the disease [
35
]. Despite the successful therapy, major concerns
were raised by the use of retroviral vectors and in particular, the Moloney leu-
kemia virus-derived vectors were found to cause lymphoproliferative disorders
during clinical trials. As an alternative strategy, Di Nunzio and co-workers have
used a self-inactivating lentiviral vector in which transgene expression is under the
control of keratin-14 that is restricted to the basal layer of the epidermis. These
