Laurel and Hardy, Peanut Butter and Jelly, Batman and Robin – can we now add iPSCs (induced pluripotent stem cells) and CRISPR to the list of famous duos? Linzhao Cheng (John Hopkins) certainly thinks so, and in a recently study his group have demonstrated how this combination of technologies may lead to an effective cell treatment for a common blood based disease.
In sickle cell disease (SCD) a hemoglobin gene mutation leads to the production of blood cells with an altered shape which causes them to block blood flow through vessels leading to pain and fatigue. The best available treatment consists of regular blood transfusions from healthy donors with matched blood types, although the body can mount an immune response to donor blood cells over time.
To get around such problems, Huang et al. used iPSCs reprogrammed from an SCD patient’s blood cells through the expression of non-integrating episomal vectors carrying reprogramming factors. They then used CRISPR gene editing technology to safely and efficiently correct the associated point mutation in the beta globin gene, noting that CRISPR mediated gene correction more efficiently than other widely used alternative techniques (ZFNs and TALENs).
Using an improved xeno-free and feeder-free culture strategy, the group then efficiently differentiated the gene-corrected iPSCs into mature blood cells which produced wild type protein in vitro. Taken as a whole, this process may allow for the production of clinical-grade patient-matched blood cells at a high enough volume to render this a therapeutically and clinically relevant strategy in the near future, replacing the need for donation from matched patients.
But why stop at SCD? The authors propose that this strategy may be relevant for other genetic blood diseases and may even extend to creating resistance to diseases such as malaria. Get a more detailed insight into this exciting new strategy at Stem Cells, February 2015.
But wait there is more! This hard working group has also published two other related articles in which they describe their ongoing effort towards bringing stem cell related therapies to the clinic (Stem Cells Transl Med, April 2015 and Stem Cells Transl Med, April 2015).