Management of severe epidermolysis bullosa by haematopoietic transplant: principles, perspectives and pitfalls.

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.