People with severe forms of epidermolysis bullosa (EB) develop widespread blistering and progressively debilitating multisystem complications that may result in a shortened lifespan. As some wounds in EB individuals are difficult or impossible to access with topical therapy, we examined the potential of systemic therapy with normal haematopoietic stem cells. In both animal models and children with EB, healthy donor cells from the haematopoietic graft migrated to the injured skin; simultaneously, there was an increase in the production of skin-specific structural proteins deficient in EB, increased skin integrity and reduced tendency to blister formation. Even though the majority of evaluable individuals have had a positive response in skin healing, frequently changing their quality of life, the improvement in lifestyle has been varied and the overall clinical response incomplete. To change the current amelioration of disease into a full cure, we propose to (i) increase safety as well as efficacy of haematopoietic cell transplant (HCT) using co-infusion of mesenchymal stromal/stem cells with haematopoietic stem cells and non-myeloablative conditioning for transplant; (ii) optimize homing of donor cells into the skin erosions in animal models of EB; and (iii) discover and test new drugs for EB therapy using patient-specific induced pluripotent stem cells. We conclude that although HCT has always been a risky treatment restricted to those with serious life-threatening or debilitating diseases, by most benchmarks, the results of HCT in EB have shown that HCT has the potential of being a durable, systemic therapy for people with severe forms of EB.Abbreviations: EB, epidermolysis bullosa; JEB-H, Herlitz variant of junctional EB; C7, type VII collagen; COL7A1, type VII collagen gene; AF, anchoring fibril; LM-332, laminin-332; LAMA3, laminin a3 gene; LAMB3, laminin b3 gene; LAMC2, laminin c2 gene; DEJ, dermal-epidermal junction; BMT, bone marrow transplantation; HCT, haematopoietic cell transplantation; GFP, green fluorescent protein; MSC, mesenchymal stem/ stromal cells; iPSC, induced pluripotent stem cells; Lin, lineage; PDGFRa, platelet-derived growth factor receptor alpha; HB-EGF, heparin-binding epidermal growth factor-like growth factor; HMGB1, high-mobility group protein B1.Key words: bone marrow -cord blood -epidermolysis bullosagenodermatosis -haematopoietic cell transplantation -regenerative medicine Accepted for publication 15 August 2012 "How wonderful that we have met with a paradox. Now we have some hope of making progress." -Niels Bohr.
Why you careThe skin is a complex, constantly changing organ that makes a boundary between us and the rest of the world. Its appearance and function allow the external affirmation of an individual and the internal freedom for self-determination. The unrelenting progression of epidermolysis bullosa (EB) destroys all of this.People with severe forms of EB develop widespread blistering and erosions shortly after birth. They can heal rapidly, but because of the unde...