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The sentinel stem cell
Since Irving Weissman’s research team reported that hematopoietic stem cells (HSCs) are known
to circulate in blood physiologically (1), functional significance of the constitutive migration has
remained elusive. A team led by Ulrich von Andrian at Harvard has recently reported in Cell (2)
an important role of circulating HSCs – to provide an immediate source to boost innate immunity.
Mature lymphocytes that circulate in blood migrate into organs and subsequently drain into
lymph for immunosurveillance. To investigate whether circulating HSCs themselves follow this
path, von Andrian’s group initially identified a HSC pool in thoracic duct lymph using both
immunotyping and serial transplantation. They also showed using pharmacological approach that
HSCs egress from extramedullary tissues into lymph in part via a Gαi-coupled S1P1 receptor.
Since HSCs also express Toll-like receptors necessary for recognition of bacterial
lipopolysaccharide (LPS), the research team implanted isolated HSCs in kidney with or without
LPS and showed that HSCs respond to LPS by actively differentiating into myeloid cells. During
differentiation, HSCs and their progenitors appear to reside within peripheral tissues as there is
lower number of implanted cells in circulation after LPS treatment. Finally, their in vitro
experiment suggests that LPS treatment slows down the mobility of HSCs and progenitors and
this correlates with the downregulation of S1P1 receptor mRNA.
Source: Fig. 7c Schematic model illustrating the trafficking of migratory HSCs and progenitors under physiological conditions and
during an inflammation (Massberg et al., 2007, Copyright, Cell Press)
This study demonstrates for the first time the role of constitutively circulating HSCs. With better
understanding of molecular players responsible for migration and homing of HSCs in the
immune system, it will be possible for us to leverage a differentiating capacity of adult stem cells
in endogenously supplying sentinel cells upon immune attack. This may obviate an inconvenient
approach to correct a defective immune system, such as T-cell immunotherapy. It also remains to
be elucidated what controls trafficking of HSCs from blood into specific organs.
Posted by Jae-Won Shin 12/02/07