Hematopoietic stem cells (HSCs) are generated in the placenta, before the circulatory system is fully operational, researchers report is this week's issue of
Cell Stem Cell. The finding offers researchers a better shot at defining the microenvironment required to grow HSCs in vitro.
Researchers have known that the placenta holds a reserve of HSCs, and had observed that when placental HSCs decline in number, the liver's reserve expands. Here, Katrin Rhodes at the University of California, Los Angeles (UCLA) and colleagues, showed that the placenta produces HSCs de novo, rather than simply acting as a "HSC kindergarten," said Hanna Mikkola from UCLA, the principal investigator of the study.
In the past, it had been difficult to determine the exact location of HSC generation, because blood circulation begins at the same stage of development that HSCs appear. The researchers used a knockout mouse that lacks a heart beat and the ability to circulate blood in order to capture HSC formation before blood flow confused the picture. They then stained for surface molecules of developing HSCs, which revealed two different HSC areas in the placenta, one that generated HSCs de novo, and another where HSCs replicated.
These results have important implications for patients, because appropriate bone marrow donors are hard to find, and the alternative, cord blood, yields a relatively low number of HSCs. Only fetal HSCs replicate into more HSCs, whereas adult HSCs differentiate into the different blood cell lineages. By learning more about the
microenvironments that nurture different stages of the HSC life-cycle, researchers hope to reproduce the signals that push HSCs into a self-regenerating program for therapy.