Bone marrow-derived stem cells may offer novel therapeutic option for skin disorder

December 05, 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.

American Society of Hematology

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	Living with Epidermolysis Bullosa by Silvia Corradin (Author) Living with Epidermolysis Bullosa has first-hand accounts written by parents and patients who are living or have lived with EB, and was compiled to help people in general understand how it is like to truly live with every form of Epidermolysis Bullosa; from the milder Simplex variants, who are nonetheless not simple to live with, to the more lethal, namely Junctional, whose patients usually succumb to before their first birthday. The stories you will read are from proud parents, or patients and their struggles and how they are coping. Some stories are sad, some are encouraging, and everything in between.
	Epidermolysis Bullosa: Clinical, Epidemiologic, and Laboratory Advances and the Findings of the National Epidermolysis Bullosa Registry by Dr. Jo-David Fine MD MPH (Editor), Dr. Eugene A. Bauer MD (Editor), Dr. Joseph McGuire MD (Editor), Dr. Alan Moshell MD (Editor) Inherited epidermolysis bullosa (EB) is a group of rare genetic diseases in which the skin is mechanically very fragile, resulting in chronic blister formation. In the most severe cases, affected persons may also experience disease involvement of other organs, cancer, and even premature death. In this book, a distinguished group of medical authorities presents the first comprehensive examination of EB employing a large, well-characterized research study population and using the latest epidemiological and biostatistical research principles. Unique to this work is its assessment of more than two thousand patients with EB, the largest such sample likely ever to be assembled in the world.In addition to state-of-the-art reviews on basic science aspects of this disease, the book contains all of...
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	Epidermolysis Bullosa: Basic and Clinical Aspects by Andrew N. Lin (Editor), D. Martin Carter (Editor) The clinical management of the rare skin disease known as epidermolysis bullosa (EB) poses a problem for those dermatologists who have never seen the disease before. All the information needed to treat patients with EB is now accessible in this practical guide written by recognized experts for the practicing physician. In a systematic and thorough fashion, the editors present the basic science necessary to understand the pathogenesis of the disease, as well as system by system coverage of the extracutaneous manifestations. This is the first volume ever to present clearly all aspects of epidermolysis bullosa in a form appropriate for use in daily clinical management.
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	Just the FACTS101 e-Study Guide for: Epidermolysis Bullosa : Pathogenesis, Diagnosis, and Management, Part II , An Issue of Dermatologic Clinics by Cram101 Never Highlight a Book Again! Just the FACTS101 study guides give the student the textbook outlines, highlights, practice quizzes and optional access to the full practice tests for their textbook.
	Complete Medical Guide For Disease Volume X; Epidermolysis Bullosa "Complete Medical Guide to Disease Volume... " are the medical books that fully researched, straight-to-the-point, easily understandable and most comprehensive medical guides for everybody. Whether you are just interested in the topic of the referring book or you are directly affected by it, these books can really help you with the information you need. Compiled by medical professionals and fully structured, this is your step toward new insights and informations. Contents What Is Epidermolysis Bullosa? Who Gets Epidermolysis Bullosa? What Causes Epidermolysis Bullosa? How Is Epidermolysis Bullosa Diagnosed? What Are the Symptoms of Epidermolysis Bullosa? How Is Epidermolysis Bullosa Treated? What Is the Value of Genetic...