2008-12-03
(WASHINGTON, December 3, 2008) – Stem cells derived from bone marrow
may serve as a novel therapeutic option to treat a disease called
epidermolysis bullosa (EB), a disorder characterized by extraordinarily
fragile skin, according to a study prepublished online in Blood, the official journal of the American Society of Hematology.
Epidermolysis bullosa is a disorder characterized by extraordinarily
fragile skin and blistering on touch, akin to third degree burns. While
the disease is often lethal in the neonatal period, more severe forms
of the disease, such as recessive dystrophic EB (referred to as RDEB),
can lead to years of painful blistering and mutilating scarring. The
condition is caused by significantly reduced collagen type 7 protein
(col7) production, a key component of the anchoring fibrils that
connect the cutaneous membranes to the dermis of the skin and mucosal
tissues in the gastrointestinal tract. A lack of these fibrils means
the dermal-epidermal connection is very sensitive, and any action,
which can include simple functions such as walking or eating, and the
touch of clothing, creates friction between the skin layers that
creates blisters and painful sores.
Children with RDEB, who are often referred to as “butterfly
children” because their skin is said to be as sensitive as butterfly
wings, develop painful skin and mucosal blistering, mutilating
scarring, alopecia (hair loss), and other erosions shortly after birth.
As a result of the extreme fragility of the skin and the chronic trauma
of friction, RDEB patients often develop squamous cell carcinomas (a
form of skin cancer). There is currently no cure for the disease, and
palliative care includes complex bandaging, surgical removal of damaged
tissue, and nutritional support.
“We have been looking into stem cells as viable treatment options
for correction of conditions such as epidermolysis bullosa, because
they can produce extracellular matrix proteins,” said Jakub Tolar, MD,
PhD, of the University of Minnesota and lead author of the study. “In
this condition, the skin, the largest organ in the body, can
significantly benefit from a renewable source of healthy cells that can
help improve the connection between the dermis and epidermis and
strengthen the skin against everyday stresses.”
In this study, researchers worked with a mouse model of RDEB-infused
bone marrow cells to determine if they would increase production of the
col7 protein and formation of anchoring fibrils, and improve survival
in the mouse recipients. The research team used bone marrow cells
enriched for hematopoietic (stem cells that can develop into most blood
cell types) and progenitor cells to increase the concentration of cells
with the capacity to produce col7. The team tested these cells against
non-enriched stem cells to determine their benefit to the treated mice.
Results of the study found that when injected into mice with RDEB,
these specially selected marrow-derived stem cells diminished the
disease process. They traveled to the diseased skin areas, increased
protein and anchoring fibrils, prevented blister formation and extended
survival. In contrast to other marrow cells, the selected cells
extended the median survival time versus untreated or non-enriched
marrow-treated recipients (10.0 versus 5.6 versus 6.0 days,
respectively). Three of the 20 mice treated with the enriched cells
benefited enough from the treatment to survive longer than the
treatment period (untreated RDEB mice usually die within two weeks).
Importantly, each survivor demonstrated marked improvement of new
blister formation (blisters develop consistently in the areas of
trauma, including footpads due to walking or in the oral cavity due to
eating) with some evidence of old blisters healing.
“Our data provide the first evidence that a selected population of
marrow cells can connect the epidermis and dermis in a mouse model of
the disease and offer a potentially valuable approach for treatment of
human RDEB and other extracellular matrix disorders. These results
provide proof of principle of bone marrow transfer to repair the
basement membrane defect in RDEB, and they warrant a clinical trial to
assess the safety and efficacy of treatment of human RDEB by means of
hematopoietic cell transplantation,” said Dr. Tolar.
Research suggests that the systemic infusion of wild-type bone
marrow cells could provide benefit to other human disorders of the
extracellular matrix. Efforts are underway to identify the requirements
of bone marrow-derived stem cells capable of efficiently homing to
wounded skin and producing an array of extracellular matrix proteins.
As the principal advantage of systemic therapy is its potential to
target not only the skin but also the mucosa of the mouth and
gastrointestinal tract, the clinical testing of efficacy of human bone
marrow for the treatment of human RDEB is underway to determine whether
it is of more substantial benefit than local protein, gene, or cellular
therapies currently being investigated by other researchers.
An estimated 50 in 1 million live births are diagnosed with EB. The
disorder occurs in every racial and ethnic group throughout the world
and affects both sexes.
Reporters who wish to receive a copy of the study or arrange an
interview with lead author Dr. Tolar may contact Patrick Irelan at
202-776-0544 or pirelan@hematology.org.
The American Society of Hematology (www.hematology.org)
is the world’s largest professional society concerned with the causes
and treatment of blood disorders. Its mission is to further the
understanding, diagnosis, treatment, and prevention of disorders
affecting blood, bone marrow, and the immunologic, hemostatic, and
vascular systems, by promoting research, clinical care, education,
training, and advocacy in hematology. In September, ASH launched Blood: The Vital Connection (www.bloodthevitalconnection.org),
a credible online resource addressing bleeding and clotting disorders,
anemia, and cancer. It provides hematologist-approved information about
these common blood conditions including risk factors, preventive
measures, and treatment options.
Blood, the official journal of the American Society of Hematology, is the most cited peer-reviewed publication in the field. Blood is issued to Society members and other subscribers twice per month, available in print and online at www.bloodjournal.org.
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