Effect of Ev.FV on Wound Healing in Dystrophic Epidermolysis Bullosa

Overview

Epidermolysis bullosa (EB) is a hereditary disease of skin tissues that causes painful bleeding blisters in the skin and mucous membrane. The prevalence of this disease is 1 in 50,000. The severity of the disease varies depending on the type of disease and may even lead to death. This disease is caused by a genetic mutation in keratin or collagen, and its incidence is the same in all men and women of different human races. In these patients, the skin becomes extremely fragile and peels off with the slightest scratch. Many blisters are one of the most obvious symptoms of this disease. The possibility of skin cancer in people suffering from this disease is more than others. Nowadays, the preference of cell therapy methods is to use biological products produced by cells such as extracellular vesicles and mitochondria instead of stem cells. The use of Extracellular vesicles and engineered EVs as messenger carriers can introduce a new treatment method based on cell products for skin regeneration and as an alternative to cell therapy. Therefore, in this study, EV.FV will be applied topically to patients.

Mesenchymal stem cell-derived EV which included Five Factors act as cell-free nanovesicles that mediate intercellular communication by transferring functional biomolecules including mRNA, microRNA, proteins, and lipids to recipient skin cells. In dystrophic epidermolysis bullosa, these exosomes facilitate wound repair and regeneration through several mechanisms: (1) modulation of inflammation by down-regulating pro-inflammatory cytokines; (2) stimulation of fibroblast and keratinocyte proliferation and migration; (3) promotion of angiogenesis via vascular endothelial growth factor (VEGF) signaling; and (4) potential delivery of collagen VII related proteins and mRNAs that support dermal epidermal junction repair. Thus, the therapeutic benefit of exosome therapy arises from paracrine signaling and molecular cargo transfer rather than cell engraftment, providing a safer and more controlled alternative to live stem cell transplantation. Our study focused on dystrophic EB (DEB), the most severe form, where loss of collagen VII disrupts anchoring fibrils and dermal-epidermal adhesion. This pathology makes DEB an appropriate target for regenerative therapies such as mesenchymal stem cell-derived EVs and investigates if EVs from MSCs are safe and effective for treating DEB. It will examine how well these exosomes help heal wounds and promote tissue regeneration, hoping to find a new biological treatment option for this challenging disease.