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Testing the Therapeutic Potential of Induced Pluripotent Stem Cells (iPSC) for Epidermolysis Bullosa Simplex (EBS) (Roop 1)

Project lead Prof Dennis Roop
Organisation University of Colorado Denver, Denver, USA
Project budget USD 240,000.00
Start date / Duration 01. Jul 2010 / 36 months
Funder(s) / Co-Funder(s) DEBRA Austria, EB MSAP/EBEP Recommended
Research area Cellular therapy

Project details

Short lay summary

Besides symptomatic care, no effective therapeutic treatment is available for EBS and other forms of EB. Therefore, a stem cell/gene therapy based approach is the only option for a permanent corrective therapy for these patients. The discovery that adult human skin cells could be reprogrammed into an embryonic stem cell (ESC)-like state has had a dramatic effect on the fields of stem cell biology and regenerative medicine. The therapeutic potential of such induced pluripotent stem cells (iPSC) for tissue repair and regeneration is enormous. This procedure not only eliminates ethical concerns associated with generating ESCs from fertilized human embryos, but it also enables the delivery of truly personalized medical treatment since the iPSC would be generated from the same individual in need of treatment. Furthermore, the therapeutic use of cells derived from a patient’s own iPSC would potentially avoid the complication of immune rejection, which might occur if cells were derived from ESCs.
However, before iPSC can be safely used in the clinic, several obstacles must be overcome. We have proposed a comprehensive set of experiments designed to address these obstacles. If we are successful in addressing the safety issues associated with using patient-specific iPSC for EBS, then this would further expand the therapeutic potential of iPSC for the treatment of other forms of EB.

What did this project achieve?

In our grant application, we proposed a comprehensive set of experiments designed to address several obstacles, and we have now achieved the following:

Aim 1:  To avoid safety concerns associated with viral vector-based reprogramming protocols, we have developed a non-genetic method for reprogramming which utilizes mRNAs encoding the four reprogramming factors (Oct3/4, Sox2, Klf4, and cMyc)

Aim 2:  We have developed a protocol for the efficient differentiation of human iPSC into a keratinocyte lineage. 

Aim 3:  To determine the genetic stability and histocompatibility of iPSC-derived keratinocytes, we have initiated experiments to compare the global transcriptome and expression pattern of imprinted genes in iPSC-derived keratinocytes vs. keratinocytes isolated from the original donor, and we are confirming their histocompatibility in an in vivo graft assay.

Aim 4:  We have developed an efficient and safe method which uses zinc-finger nuclease (ZFN)-mediated technology to inactivate the mutant keratin 14 (KRT14) gene in iPSC generated from an EBS patient with the Dowling-Meara hot spot mutation R125C.


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