Latest FIRST funded Research on Regenerative Medicine & Stem Cell Biology
As one might imagine, the most top-of-mind question FIRST is asked by nearly all those affected with ichthyosis is: What type of research is FIRST currently funding? And, in fact, one of the most rewarding and exciting parts of our jobs, is…providing the answer.
Since 2006, Dr. Dennis Roop, an internationally recognized leader in skin disease research and his team at the Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology at the University of Colorado, has been funded by FIRST research grants to continue their cutting-edge work in epidermolytic ichthyosis (formerly known as EHK).
Traditionally, stem cell research has focused on cells that are isolated from embryos and have unlimited “pluripotentcy” (the potential to differentiate into any type of cell or tissue). However, the goal for Dr. Roop’s project is to generate induced or “reprogrammed,” pluripotent stem (iPS) cells, from adult cells.
Dr. Roop is specifically working with adult cells of epidermolytic ichthyosis (EI) patients – essentially reprogramming, or “inducing” pluripotentcy, by introducing factors, into these cells, that are capable of removing all of the cell’s memory, stripping it of all genetic coding as an adult cell, and reverting that cell back to an embryonic-like state. The reprogramming procedure gives the adult cells nearly the same pluripotent capabilities as embryonic stem cells. There are two advantages of working with iPS compared to adult cells: they can multiply for a more prolonged time than adult cells and gene correction strategies work more efficiently in iPS cells than in adult cells.
The long-term goal of Roop’s work is to create iPS cells from individual patients, correct the mutant gene they contain, differentiate the iPS cells into keratinocytes andthen graft the corrected keratinocytes back onto the patient–in hopes that they will multiply and generate unaffected skin. The research is best described in the above video, taken September 2012, whereby the fascinating research of Dr. Roop and his team is explained to a family affected by EI, in the very clinic the research is being conducted.
What specific progress has been made?
To date, the defective K1 gene in one patient’s iPS cells has been corrected. This was achieved by introducing a zinc finger nuclease and a piece of DNA that contains the normal version of the mutant K1 gene into the iPS cells. The zinc finger nucleases are like molecular scissors that cut the K1 gene near the site of the mutation. The cells own DNA repair machinery then replaces the cut, defective region of the K1 gene with the introduced normal region of the K1 gene.
Tests are currently being performed on the corrected iPS cells to make sure that they are genetically stable and contain no new mutations. Once that has been confirmed, a special recipe of nutrients will be added to the corrected iPS cells to allow them to become keratinocyte stem cells, and those will then be grafted onto mice to see if they will form a normal epidermis. Differentiating iPS cells into keratinocytes is routine in many labs and well-established in Roop’s lab.