Scientists have discovered a way to convert human skin cells into transplantable white blood cells via stem cells.
An exciting new report issued from the Salk Institute discusses a new method that can turn human skin cells into disease-fighting white blood cells. In the last few years, the potential and promise of induced pluripotent stem cells (iPSCs) have taken the cellular therapy world by storm. But as the initial excitement waned and the hard work of translating basic research into successful therapies began, it became evident that it was going to be difficult to live up to such high expectations. A collaborative effort between top researchers at the Salk Institute for Biological Studies in San Diego and the Center of Regenerative Medicine in Barcelona could change all that.
Making induced pluripotent stem cells is notoriously tedious; it takes at least two months to produce, characterize, and differentiate these cells. Furthermore, the process is highly inefficient:-On average, only about 1% of the cells that are de-differentiated will become pluripotent stem cells. Once iPSCs make it to the clinic, there are other hurdles to overcome. The cells do not engraft well into organs or bone marrow, and transplant treatment can sometimes induce secondary tumors.
The authors explain that their new method circumvents many of the problems associated with re-programming human cells. Unlike previous techniques that reverse human fibroblasts (skin cells) all the way back to a pluripotent state, the method, known as “indirect linage conversion,” uses just two molecules to convert cells back into an intermediate state between true pluripotent stem cells and white blood cells. In order to do this, Dr. Pulecio and his colleagues overexpress a transcription factor called Sox2 within the skin cells. Sox2 basically induces memory loss in the cells, allowing them to forget their skin cell programming and become more adaptable.
Once the cells regress to this state, a short molecule known as miR-125b is used to induce the cells to become white blood cell precursors. This part of the process is called “lineage specification” and is unique in that the partially committed cells need to be exposed to cytokines and other factors present in vivo to complete their differentiation. This means that it is only when cells are transplanted into their recipient (in this case a mouse) will they complete the process of maturing into white blood cells. The whole process takes just two weeks, does not produce tumors, and engrafts well in these preliminary studies carried out in mice.
The researchers are currently conducting toxicology studies, as well as additional transplant studies, with the aim of taking the method to pre-clinical trials in the near future. They hope that their studies will bypass the risks associated with the use of pluripotent stem cells and lead to the development of novel clinical therapies. “It is fair to say that the promise of stem cell transplantation is now closer to realization,” study co-author Ignacio Sancho-Martinez said in a news release.
HemaCare applauds such novel research and is proud to be a supplier of stem cells.
 Pulecio J, et al. Conversion of Human Fibroblasts into Monocyte-Like Progenitor Cells. Stem Cells, June 2014. Epub ahead of print.