Translating a Stem Cell-Based Therapy for Epidermolysis Bullosa into the Clinic
[Technical Report, Annual Report]
University of Colorado Denver
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This proposal is developing a stem-cell based therapy for recessive dystrophic epidermolysis bullosa RDEB, which is one of the most severe forms of epidermolysis bullosa EB, a group of rare inherited skin blistering diseases. To accomplish this goal, we are utilizing genetic correction of patient-specific induced pluripotent stem cells iPSCs followed by the differentiation of these corrected iPSCs into epidermal cells and fibroblasts for the generation of composite full thickness skin grafts for transplantation. During this funding period, we completed our studies on reproducibility of our simultaneous gene editing and reprogramming protocol for the generation of gene corrected RDEB iPSCs. We successfully generated gene corrected RDEB iPSCs from three patients and completed characterization of these iPSC lines on a molecule level. We initiated functional validation of keratinocytes derived from these genetically corrected RDEB iPSCs. In our preliminary analysis, keratinocytes derived from gene corrected RDEB iPSCs show the restoration of the expression of type VII collagen and the formation of a basement membrane in 3D skin equivalents. We also continue working with our cGMP-compliant facility to advance our protocols toward clinical manufacturing. As indicated in the previous report, the initiation of many in vivo studies was delayed due to the COVID-19 pandemic and the closure of research laboratories on the University of Colorado Anschutz Medical Campus. While the University allowed research activities to resume on July 1, research personnel are required to work on a staggered basis, with no more than 50 occupancy at any given time to maintain social distancing. These restrictions continue to impact our research progress. The potential delay caused by these restrictions will be mitigated by requesting a no cost extension before the completion of Year 3 of the project.
- Medicine and Medical Research