Hematopoietic stem cell mobilization: updated conceptual renditions

Abstract

Despite its specific clinical relevance, the field of hematopoietic stem cell mobilization has received broad attention, owing mainly to the belief that pharmacologic stem cell mobilization might provide clues as to how stem cells are retained in their natural environment, the bone marrow ‘niche’. Inherent to this knowledge is also the desire to optimally engineer stem cells to interact with their target niche (such as after transplantation), or to lure malignant stem cells out of their protective niches (in order to kill them), and in general to decipher the niche’s structural components and its organization. Whereas, with the exception of the recent addition of CXCR4 antagonists to the armamentarium for mobilization of patients refractory to granulocyte colony-stimulating factor alone, clinical stem cell mobilization has not changed significantly over the last decade or so, much effort has been made trying to explain the complex mechanism(s) by which hematopoietic stem and progenitor cells leave the marrow. This brief review will report some of the more recent advances about mobilization, with an attempt to reconcile some of the seemingly inconsistent data in mobilization and to interject some commonalities among different mobilization regimes.

Extracellular molecules in hematopoietic stem cell mobilisation

“…The need for increased S1P in the blood and the involvement of S1P in G-CSFmediated mobilization are not clear reported to have chemotactic effects on HSPC [99]. However, humans treated with either noradrenalin reuptake inhibitors or β-receptor blockers mobilize with equivalent efficiency as untreated donors [103]. This suggests that there could be differences between the human and murine systems, or alternatively that the long-term administration of these agents for chronic conditions may result in adaptive changes that counter the effect.…”

Identification and Characterization of Circulating Variants of CXCL12 from Human Plasma: Effects on Chemotaxis and Mobilization of Hematopoietic Stem and Progenitor Cells

“…FDCP-mix multipotent murine hematopoietic progenitor cells (clone A4) were obtained from C. Heyworth and E. Spooner (Christie Hospital, Paterson Institute, Manchester, United Kingdom) and maintained in Iscove's modified Dulbecco's medium (IMDM) that was supplemented with 20% (vol/vol) horse serum (HS) and 10 ng/mL rmIL-3 (R&D Systems) at 37°C in 5% CO 2 . The cells were passaged thrice a week to a cell concentration of 2 · 10 5 cells/ mL and maintained at 37°C/5% CO 2 .…”

“…HPC mobilization is co-regulated by a wide range of stressors, including DNA damage, chemotherapeutic drugs, cytokines, and chemokines such as CXCL8 [interleukine-8 (IL-8)], CXCL1 [growth-regulated oncogene alpha (GROa)], and CXCL12 [stromal-derived factor-1a (SDF-1a)]. These cytokines and chemokines, along with bioactive lipids such as sphingosine-1-phosphate and ceramide-1-phosphate, together with complement factors may also have a significant impact on the homing of circulating and transplanted HPCs and their engraftment in the bone marrow (BM) [1][2][3].…”

The Hematopoietic Chemokine CXCL12 Promotes Integration of Human Endothelial Colony Forming Cell–Derived Cells into Immature Vessel Networks

“…Interactions of CXCR4 with CXCL12 can be inhibited by CXCR4 antagonists, which include the bicyclam AMD3100 [12,13], used therapeutically as an effective mobilizer of HSC/HPCs from bone marrow in patients refractory to G-CSF mobilization [12][13][14][15]. AMD3100 mobilizes human endothelial progenitor cells and proangiogenic cells into the peripheral blood in both the human and mice, although, in the murine studies, both endothelial and stromal progenitor cell mobilization was enhanced by VEGF pretreatment [16,17].…”