Related Experiment Video
Updated: Jun 12, 2025
10:40
Homing of Hematopoietic Cells to the Bone Marrow
Published on: March 18, 2009
29.4K
CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow
Stephanie N Hurwitz1,2, Danielle R Kobulsky2, Seul K Jung2
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Science Advances
|September 18, 2024
Summary
Hematopoietic stem and progenitor cell (HSPC) extracellular vesicles (EVs) remodel bone marrow endothelial cells. This process enhances HSPC homing and engraftment via CCR2 ligand pathways, offering new transplantation strategies.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Hematopoietic stem and progenitor cell (HSPC) homing and engraftment are crucial for bone marrow transplantation success.
- Endothelial cell (EC) adaptation in the bone marrow microenvironment is vital for HSPC occupancy, but underlying signals are unclear.
- Extracellular vesicles (EVs) are key mediators of intercellular communication, influencing tissue microenvironments.
Purpose of the Study:
- To investigate the role of HSPC-derived extracellular vesicles (EVs) in modulating bone marrow endothelial cells (ECs) and promoting HSPC homing.
- To elucidate the molecular mechanisms by which HSPC EVs influence ECs and subsequent HSPC engraftment.
- To explore the potential of HSPC EVs as a therapeutic strategy for improving hematopoietic stem cell transplantation outcomes.
Main Methods:
- Utilized murine models to study the interaction between HSPC EVs and bone marrow ECs.
- Investigated the targeting of ECs by HSPC EVs via integrin α4β7.
- Analyzed the induction of C-C motif chemokine receptor 2 (CCR2) ligands in ECs by HSPC EVs.
- Assessed the synergistic effects of CCR2 ligands with CXCL12-CXCR4 signaling on HSPC homing.
- Evaluated the efficacy of marrow preconditioning with HSPC EVs or CCR2 ligands in non-irradiated murine transplantation models.
Main Results:
- Demonstrated that integrin α4β7 on HSPC EVs mediates their uptake into bone marrow ECs.
- Showed that HSPC EVs induce the upregulation of CCR2 ligands in ECs.
- Confirmed that these induced CCR2 ligands synergize with CXCL12-CXCR4 signaling to enhance HSPC homing to the bone marrow.
- Established that preconditioning with HSPC EVs or CCR2 ligands improves homing and early graft occupancy in transplantation models.
Conclusions:
- Identified a novel mechanism where HSPC EVs remodel bone marrow ECs to facilitate HSPC engraftment.
- Defined a new role for CCR2-dependent signaling pathways in governing graft homing.
- Proposed HSPC EVs and CCR2 ligands as potential therapeutic agents for enhancing hematopoietic stem cell transplantation success.
More Related Videos
11:06Combining Intravital Fluorescent Microscopy IVFM with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
Published on: March 21, 2017
7.9K
10:03Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging
Published on: August 1, 2017
11.7K
Related Concept Videos
01:01Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
01:21Hematopoiesis
5.2K
The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
5.2K
01:19Multipotency of Hematopoietic Stem Cells
3.0K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.0K
01:28Role of Hematopoietic Growth Factors
1.3K
Hematopoietic growth factors are molecules that regulate the differentiation rate of hematopoietic stem cells (HSCs). Erythropoietin (EPO), primarily produced by the kidneys, plays a crucial role in erythrocyte production. When oxygen levels in the blood are low, EPO is released into the bloodstream, reaching the bone marrow, where it stimulates HSCs to differentiate and mature into erythrocytes, which are vital for oxygen transport.
Thrombopoietin (TPO), mainly released by the liver,...
Thrombopoietin (TPO), mainly released by the liver,...
1.3K
01:21Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
01:15Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K