Self-repopulating recipient bone marrow resident macrophages promote long-term hematopoietic stem cell engraftment

Area of Science:

• Immunology
• Hematology
• Stem Cell Biology

Background:

• Resident tissue macrophages play key roles in maintaining the hematopoietic stem cell niche and supporting erythropoiesis.
• Understanding macrophage subset dynamics post-transplantation is critical for improving hematopoietic stem cell transplantation (HSCT) outcomes.

Purpose of the Study:

• To investigate the persistence and function of distinct bone marrow and splenic macrophage subsets after lethal irradiation and autologous HSCT in mice.
• To determine the role of recipient-derived macrophages in hematopoietic reconstitution and stem cell engraftment.

Main Methods:

• Utilized a myeloid reporter gene (Csf1r-eGFP) to track macrophage populations in a mouse model.
• Analyzed macrophage subset survival and repopulation kinetics in bone marrow and spleen post-HSCT.
• Assessed the impact of selective CD169+ macrophage depletion on stem cell engraftment and hematopoietic reconstitution.

Main Results:

• Multiple recipient macrophage subsets exhibited organ-specific survival and persistence post-HSCT.
• Bone marrow CD169+ resident macrophages and erythroid-island macrophages self-repopulated long-term through cell division.
• Depletion of recipient CD169+ macrophages significantly impaired long-term HSC engraftment and overall hematopoietic reconstitution.

Conclusions:

• Recipient bone marrow resident macrophages, particularly CD169+ cells, are essential for optimal HSCT success.
• These macrophages are critical for the engraftment of long-term reconstituting HSCs.
• Targeting or preserving recipient macrophages could be a valuable strategy for enhancing HSCT therapies.