Sara Howden and her colleagues at the Morgridge Institute for Research and the Murdoch Children’s Research Institute in Australia have devised a protocol that can significantly decrease the time involved in reprogramming mature adult cells while genetically repairing them at the same time. Such an advance is essential for making future therapies possible.
Howden and others demonstrated that genetically repaired cells can be derived from patient skin cells in as little as two weeks. This is much shorter than the multistep approaches that take more than three months.
How were they able to shorten the time necessary to do this? They combined two integral steps in the procedure. Adult cells were reprogrammed to an embryonic stem cell-like state in order to be differentiated into the cells that we want. Secondly, the cells must undergo gene editing in order to correct the disease-causing mutation.
By in this new protocol developed by Howden and her colleagues, they combined the reprogramming and gene editing steps.
To test their new protocol, Howden and her team used cells isolated from a patient with an inherited retinal degeneration disorder, and an infant with severe immunodeficiency. In both cases, the team not only derived induced pluripotent stem cell lines from the adult cells of these patients, but they were also able to repair the genetic lesion that causes the genetic disease.
This protocol might advance transplant medicine by making gene-correction therapies available to patients in a much timelier fashion and at lower cost.
Presently, making induced pluripotent stem cell lines from a patient’s cells, genetically repairing those cells, expanding them, differentiating them, and then isolating the right cells from transplantation, while checking the cells all along the way and properly characterizing them for safety reasons would take too long and cost too much.
With this new approach, however, Howden and others used the CRISPR/Cas9 technology to edit the damaged genes while reprogramming the cells, greatly reducing the time required to make the cells for transplantation.
Faster reprogramming also decreases the amount of time the cells remain in culture, which minimizes the risks of gene instability or epigenetic changes that can sometimes occur when culturing cells outside the human body.
Howden’s next goal is to adapt her protocol to work with blood cells so that blood samples rather than skin biopsies can be used to secure the cells for reprogramming/gene editing procedure. Blood cells also do not require the expansion that skin cells require, which would even further shorten the time needed to make the desired cell types.
The accelerated pace of the reprogramming procedure could make a genuine difference in those cases where medical interventions are required in as little time as possible. For example, children born with severe combined immunodeficiency usually die within the first few years of life from massive infections.
Howden cautioned, however, that she and her team must first derive a long-term source of blood cells from pluripotent stem cells before such treatments are viable and demonstrate the safety of such treatments as well.
See Stem Cell Reports, 2015: DOI: 10.1016/j.stemcr.2015.10.009.