If you have been following this blog and keeping up with the fascinating world of regenerative medicine, you know that all adult stem cells are not the same. There are different progenitor cell types like Hematopoietic stem cells (HSCs) and Mesenchymal stem cells (MSCs) that are derived from bone marrow. HSCs give rise to all the cells in the blood, including immune cells like B cells and T cells, through the process of hematopoiesis and here is an excellent review on MSCs and the therapeutic benefits they provide.

There is a constant need for blood/blood components

There is a huge demand for blood to treat common blood disorders including anemia, bleeding disorders such as hemophilia and blood cancers such as leukemia, lymphoma and myeloma. Now what if scientists were to address this need by growing hematopoietic stem cells (that will repopulate all the cells present in the blood) in a laboratory environment? Unfortunately, years of research and failed attempts have taught the scientific community that there are several hurdles to the de novo (starting anew) generation of hematopoietic stem cells (HSCs). These include determining what transcription factors (proteins that bind to DNA and turn on/turn off genes) are required to maintain commitment to a hematopoietic lineage and what the ideal culture protocols or assay methods are to sustain HSCs.

Finally…a breakthrough!

Which is why this study by Lis et al., is so important! They showed that the transient (lasting only for a short time) expression of four transcription factors, FGRS (FGRS: Fosb Gfil, Runx1 and Spi1) in adult mouse endothelial cells reprogrammed the cells into engraftable HSCs. The researchers then proved that these are bonafide HSCs, since these cells were capable of self-renewal and differentiation into all the different types of cells of hematopoietic lineage.

In another study, by Sugimura et al., they used a different approach to generate HSCs. Here, they converted adult skin cells to produce induced pluripotent stem cells (iPSCs, genetically reprogrammed cells) which were then used to generate the HSCs in mice. While procuring skin cells to generate the iPSCs is relatively easy, the intermediate pluripotent state of the cells increases the risk of cancer formation, making this method less desirable. In contrast, Lis et al., successfully generated HSCs using adult stem cells without passing through a “potentially pro-oncogenic pluripotent state”, thus minimizing the risk of cancer formation.

Future Direction

What we have learned from these studies is that we are most certainly one step closer to utilizing hematopoietic stem cells generated in the laboratory for treating patients. There is an obvious benefit to using a patient’s own cells (endothelial cells or skin cells) to generate HSCs, since this eliminates the risk of immune rejection. Cells from universal donors could be “grown” in the laboratory to boost the blood supply for use in the field of medicine. Red blood cell (RBC) generation will most likely be the first step since these are anucleate, which means potentially no cell division occurs thus minimizing the risk of DNA mutations and cancer formation. These manufactured RBCs would be highly beneficial in treating blood disorders and in blood transfusions. However, demonstrating the safety of these laboratory-grown cells is essential and will require clinical trials and testing before this can become a universally adopted practice.