The sentinel stem cell

by on December 2, 2007 · 0 comments

in Journal club, niche

Blogging on Peer-Reviewed ResearchSince Irving Weissman’s research team reported that hematopoietic stem cells (HSCs) are known to circulate in blood physiologically, functional significance of the constitutive migration has remained elusive. A team led by Ulrich von Andrian at Harvard University (Boston, MA) has recently reported in Cell journal 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.

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Schematic model illustrating the trafficking of migratory HSCs and progenitors under physiological conditions and during an inflammation (Source: Massberg et al., 2007

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.

Immunosurveillance by Hematopoietic Progenitor Cells Trafficking through Blood, Lymph, and Peripheral Tissues. Cell 2007; 131: 994-100

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