Placenta as a site for hematopoietic stem cell development

The discovery of a major hematopoietic stem cell (HSC) pool in mid-gestation mouse placenta has defined the placenta as yet another important anatomical site that participates in HSC development. Placental HSC activity starts in parallel with the AGM region, before HSCs are found in circulation or have colonized the fetal liver. Moreover, placental hematopoietic activity culminates in a rapid expansion of the definitive HSC pool, which occurs during the time when the fetal liver HSC reservoir begins to grow. Furthermore, hematopoietic cells in mid-gestation mouse placenta are not instructed for differentiation along the myeloerythroid lineage, as in the fetal liver. These findings suggest that the placenta provides a supportive niche where the definitive hematopoietic stem cell pool can be temporarily established during development. Future studies are needed to characterize the developmental events that lead to the establishment of placental HSC pool, and to define the microenvironmental signals that support this process. Furthermore, if the stem cell–promoting properties of the placental niche can be harnessed in vitro to support HSC formation, maturation, and/or expansion in culture, these assets may greatly improve hematopoietic stem cell–based therapies in the future.