Peripheral blood stem cell mobilization: new regimens, new cells, where do we stand.
OBJECTIVE
Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells are widely used to reconstitute hematopoiesis; however, preclinical and clinical studies show that improvements to this mobilization can be achieved. We discuss the development of new mobilizing regimens and evaluation of new findings on mobilized stem cell populations that may improve the utility and convenience of peripheral blood stem cell transplant.


RESULTS
Chemokines and their receptors regulate leukocyte trafficking, and altering chemokine signaling pathways mobilizes stem cells. In recent trials, combination use of the chemokine (C-X-C motif) receptor 4 antagonist AMD3100 and granulocyte colony-stimulating factor mobilized more CD34 cells in fewer days than granulocyte colony-stimulating factor alone and allowed more patients to proceed to autotransplant. In preclinical studies the chemokine GRObeta synergizes with granulocyte colony-stimulating factor and when used alone or with granulocyte colony-stimulating factor mobilizes more primitive hematopoietic stem cells with less apoptosis, higher integrin activation, lower CD26 expression and enhanced marrow homing compared with granulocyte colony-stimulating factor. Hematopoietic stem cells mobilized by GRObeta or AMD3100 demonstrate superior engraftment and contribution to chimerism in primary and secondary transplant studies in mice, and peripheral blood stem cells mobilized by AMD3100 and granulocyte colony-stimulating factor in patients demonstrate enhanced engraftment capabilities in immunodeficient mice.


CONCLUSIONS
Alternate regimens differentially mobilize stem cell populations with unique intrinsic properties with the potential to expand the utility of hematopoietic transplantation. Continued mechanistic evaluation will be critical to our understanding of mechanisms of mobilization and their use in regenerative medicine.
Pelus
Louis M
LM
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. lpelus@iupui.edu
D000818:Animals; D019743:Chemokines, CXC / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods* / Q000639:trends; D006801:Humans; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D054387:Receptors, CXCR / Q000037:antagonists & inhibitors
D019743:Chemokines, CXC; D054387:Receptors, CXCR