Completed Projects, Gene Therapy, Whole Body Treatment
About This Project

Mensenchymal stromal cells engineered to express Collagen VII for the treatment of Recessive Dystrophic Epidermolysis Bullosa

Lay summary

Mesenchymal stromal cells (MSCs) are adult stem cells which can transform into other types of cells. In this project, MSCs taken from patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB) were genetically modified to express Collagen VII and tested on animal models.

The aim of the project was to assess the ability to manufacture and successfully deliver genetically modified MSCs as a systemic (whole body treatment) for RDEB.

Unfortunately, systemic delivery of these Collagen VII producing cells resulted in accumulation in the lungs, rather than in the skin, so further work is required to develop a successful systemic treatment for RDEB.

Scientific Summary

This project built on experience derived from the Lenticol F project. Feasibility and safety data will inform development of a systemic therapy using engineered MSCs.

The study engineered MSCs to over-express Collagen VII and then analysed the effects of intravenous injection for correction of human skin grafts on immunodeficient mice.

Overall, there was no evidence that systemically injected genetically engineered MSCs migrated to the sites of skin grafts – most appeared to be rapidly (within 1 hour of injection) sequestered during passage through the lungs.

Related Publications

Petrova A. et al. Human Mesenchymal Stromal Cells Engineered to Express Collagen VII Can Restore Anchoring Fibrils in Recessive Dystrophic Epidermolysis Bullosa Skin Graft Chimeras. Journal of Investigative Dermatology 2019;140(1):121-131