Hematopoietic stem cell trafficking: regulated adhesion and attraction to bone marrow microenvironment

Area of Science:

• Hematology
• Stem Cell Biology
• Bone Biology
• Neuroendocrinology

Background:

• Hematopoiesis, or blood formation, primarily occurs within bone cavities, indicating the influence of bone-derived factors.
• Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow and can be mobilized to circulation.
• Mobilization involves agonists that alter chemokine CXCL12 and adhesion molecule function, crucial for cell migration.

Purpose of the Study:

• To review emerging concepts regarding the mechanisms of stem cell migration from bone marrow.
• To explore the role of bone-derived factors and signaling pathways in hematopoietic stem cell mobilization.
• To discuss the impact of Granulocyte colony-stimulating factor (G-CSF) on osteoblast function and its potential link to the sympathetic nervous system (SNS).

Main Methods:

• This is a review article, synthesizing findings from recent studies.
• It focuses on analyzing the molecular and cellular mechanisms underlying HSPC mobilization.
• The review examines the interplay between bone marrow microenvironment, G-CSF, and the SNS.

Main Results:

• Granulocyte colony-stimulating factor (G-CSF), a key drug for HSPC mobilization, significantly suppresses osteoblast activity.
• Evidence suggests that G-CSF-induced suppression of osteoblasts is mediated by signals from the sympathetic nervous system (SNS).
• Alterations in CXCL12 chemokine and adhesion molecule expression/function are central to HSPC migration.

Conclusions:

• Bone marrow's role in hematopoiesis is intrinsically linked to bone-derived factors influencing stem cell behavior.
• The sympathetic nervous system (SNS) plays a critical role in regulating G-CSF's effects on bone and stem cell mobilization.
• Understanding these complex interactions is key to developing novel strategies for stem cell mobilization and bone health.