Under physiological conditions, mature hematopoietic cells freely circulate in the peripheral blood, while immature hematopoietic stem and progenitor cells (HSPCs) mostly reside in unique microenvironments, or niches, in the bone marrow (BM). However, in stress situations, such as infection, inflammation, bleeding, or neutropenia, activated HSPCs detach from their BM niche and enter the circulation in a process called mobilization.
Mobilization can also be induced pharmacologically to treat chemotherapy-induced neutropenia or collect HSPCs for transplantation. This is most often achieved with granulocyte-colony stimulating factor (G-CSF), but can also be done with targeted inhibition of the bond between HSPCs and their niche, such as with a CXCR4 antagonist (plerixafor).
Unfortunately, in many cases, our current mobilization approaches are inadequate in correcting neutropenia or mobilizing HSPCs to the periphery. Moreover, although mobilized stem cell transplants lead to faster hematopoietic reconstitution, they are also associated with increased risk of graft-versus-host disease (GVHD) in recipients.
The goal of this collection of articles is to advance our understanding of the mechanism of hematopoietic cell mobilization, including mature, progenitor, and stem populations, and to develop safer and more effective mobilization approaches for the collection of HSPCs for transplantation and treatment of chemotherapy-related neutropenia. Although significant work has been done to understand the role and function of recombinant G-CSF in these applications, investigations into new molecular targets involved in mobilization have been lacking. Moreover, our understanding of the chemical and cellular characteristics of different niches in the BM, mechanisms by which cells attach and detach from their niches, functional difference between mobilized and non-mobilized HSPCs, and long-term side effects of mobilizing therapy is incomplete. These studies can help not only with the development of novel therapies for HSPC mobilization and neutropenia treatment, but also optimize the cell composition of mobilized blood to maximize reconstitution potential and graft-versus-leukemia (GVL) while minimizing GVHD.
In this Research Topic, we would like to include articles in the form of Original Research, Review/Opinion/Perspective and Clinical Trial/Case Report, that relate to, but are not limited to, the following topics:
- New drugs for mobilization of HCS and/or treatment of neutropenia
- Insights into the interactions of hematopoietic progeny, progenitor, and stem cells with their niche
- Functional comparison of mobilized versus non-mobilized hematopoietic cells
- Molecular targets for inducing mobilization
- Mechanisms of mobilization
- Novel applications of existing drugs
- Challenges in the clinical use of mobilization, including mobilization failure and GVHD
Under physiological conditions, mature hematopoietic cells freely circulate in the peripheral blood, while immature hematopoietic stem and progenitor cells (HSPCs) mostly reside in unique microenvironments, or niches, in the bone marrow (BM). However, in stress situations, such as infection, inflammation, bleeding, or neutropenia, activated HSPCs detach from their BM niche and enter the circulation in a process called mobilization.
Mobilization can also be induced pharmacologically to treat chemotherapy-induced neutropenia or collect HSPCs for transplantation. This is most often achieved with granulocyte-colony stimulating factor (G-CSF), but can also be done with targeted inhibition of the bond between HSPCs and their niche, such as with a CXCR4 antagonist (plerixafor).
Unfortunately, in many cases, our current mobilization approaches are inadequate in correcting neutropenia or mobilizing HSPCs to the periphery. Moreover, although mobilized stem cell transplants lead to faster hematopoietic reconstitution, they are also associated with increased risk of graft-versus-host disease (GVHD) in recipients.
The goal of this collection of articles is to advance our understanding of the mechanism of hematopoietic cell mobilization, including mature, progenitor, and stem populations, and to develop safer and more effective mobilization approaches for the collection of HSPCs for transplantation and treatment of chemotherapy-related neutropenia. Although significant work has been done to understand the role and function of recombinant G-CSF in these applications, investigations into new molecular targets involved in mobilization have been lacking. Moreover, our understanding of the chemical and cellular characteristics of different niches in the BM, mechanisms by which cells attach and detach from their niches, functional difference between mobilized and non-mobilized HSPCs, and long-term side effects of mobilizing therapy is incomplete. These studies can help not only with the development of novel therapies for HSPC mobilization and neutropenia treatment, but also optimize the cell composition of mobilized blood to maximize reconstitution potential and graft-versus-leukemia (GVL) while minimizing GVHD.
In this Research Topic, we would like to include articles in the form of Original Research, Review/Opinion/Perspective and Clinical Trial/Case Report, that relate to, but are not limited to, the following topics:
- New drugs for mobilization of HCS and/or treatment of neutropenia
- Insights into the interactions of hematopoietic progeny, progenitor, and stem cells with their niche
- Functional comparison of mobilized versus non-mobilized hematopoietic cells
- Molecular targets for inducing mobilization
- Mechanisms of mobilization
- Novel applications of existing drugs
- Challenges in the clinical use of mobilization, including mobilization failure and GVHD