Skin layer grown from human stem cells could replace animals in
drug and cosmetics testing.
An international team led by King's College London and the San
Francisco Veteran Affairs Medical Center (SFVAMC) has developed the
first lab-grown epidermis - the outermost skin layer - with a
functional permeability barrier akin to real skin. The new
epidermis, grown from human pluripotent stem cells, offers a
cost-effective alternative lab model for testing drugs and
cosmetics, and could also help to develop new therapies for rare
and common skin disorders.
The epidermis, the outermost layer of human skin, forms a
protective interface between the body and its external environment,
preventing water from escaping and microbes and toxins from
entering. Tissue engineers have been unable to grow epidermis
with the functional barrier needed for drug testing, and have been
further limited in producing an in vitro (lab) model for
large-scale drug screening by the number of cells that can be grown
from a single skin biopsy sample.
The new study describes the use of human induced pluripotent
stem cells (iPSC) to produce an unlimited supply of pure
keratinocytes - the predominant cell type in the outermost layer of
skin - that closely match keratinocytes generated from human
embryonic stem cells (hESC) and primary keratinocytes from skin
biopsies. These keratinocytes were then used to manufacture 3D
epidermal equivalents in a high-to-low humidity environment to
build a functional permeability barrier, which is essential in
protecting the body from losing moisture, and preventing the entry
of chemicals, toxins and microbes.
A comparison of epidermal equivalents generated from iPSC, hESC
and primary human keratinocytes (skin cells) from skin biopsies
showed no significant difference in their structural or functional
properties compared with the outermost layer of normal human
skin.
Dr Theodora Mauro, leader of the SFVAMC team, said: "The ability
to obtain an unlimited number of genetically identical units can be
used to study a range of conditions where the skin's barrier is
defective due to mutations in genes involved in skin barrier
formation, such as ichthyosis (dry, flaky skin) or atopic
dermatitis. We can use this model to study how the skin barrier
develops normally, how the barrier is impaired in different
diseases and how we can stimulate its repair and recovery."
Dr Dusko Ilic, leader of the team at King's College London,
said: "Our new method can be used to grow much greater quantities
of lab-grown human epidermal equivalents, and thus could be scaled
up for commercial testing of drugs and cosmetics. Human epidermal
equivalents representing different types of skin could also be
grown, depending on the source of the stem cells used, and could
thus be tailored to study a range of skin conditions and
sensitivities in different populations."
The paper, 3D In Vitro Model of a Functional Epidermal Permeability Barrier
from Human Embryonic Stem Cells and Induced Pluripotent Stem
Cells, is published in Stem Cell Reports.