Stem-cell Based Therapies for Epidermolysis Bullosa
Abstract
This application addresses the FY11 PRMRP Topic Area, Epidermolysis Bullosa, and proposes to develop stem-cell based therapies for junctional epidermolysis bullosa (JEB), 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 proposing to develop stem-cell based therapies for EB using autologous induced pluripotent stem cells (iPSCs) derived from skin cells harvested from the same EB patient. We hypothesize that using a combination of genetically corrected patient-specific iPSC-derived keratinocyte stem cells for skin grafting in combination with iPSC-derived hematopoietic and mesenchymal stem cells for transplantation will be effective in correcting both lesions within the skin as well as in mucosal epithelia. During the first year of funding, we were able to successfully cross IRG mice with JEB mice to obtain IRGRFP/LAMA3fl/wt/K14-Cre.ER mice, which can now be used for the immunological studies proposed in the initial application. We also generated iPSCs from these mice using hSTEMCCA-loxP lentivirus to address the possibility of gene correction via ZFNs in these cells. In addition, we accomplished a major breakthrough by adapting a mRNA reprogramming protocol for the generation of iPSCs from human keratinocytes. This reprogramming protocol can now be employed to generate iPSCs not only from JEB patients but also from patients with other inherited skin diseases, as well as veterans with chronic wounds.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA606018
Entities
People
- Dennis Roop
- Jakub Tolar
Organizations
- University of Minnesota