title: No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice.
abstract: Gene therapy for sickle cell disease is currently in active trials. Collecting hematopoietic progenitor cells safely and effectively is challenging, however, because granulocyte colony stimulating factor, the drug used most commonly for mobilization, can cause life-threatening vaso-occlusion in patients with sickle cell disease, and bone marrow harvest requires general anesthesia and multiple hip bone punctures. Plerixafor is an inhibitor of the CXCR4 chemokine receptor on hematopoietic progenitor cells, blocking its binding to SDF-1 (CXCL12) on bone marrow stroma. In support of a clinical trial in patients with sickle cell disease of plerixafor mobilization (NCT02193191), we administered plerixafor to sickle cell mice and found that it mobilizes hematopoietic progenitor cells without evidence of concomitant cell activation or brain vaso-occlusion.
authors: Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10065, United States.
authors: Erika
authors: E
authors: Choi
authors: Department of Radiology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States.
authors: Craig
authors: C
authors: Branch
authors: Department of Radiology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States.
authors: Min-Hui
authors: MH
authors: Cui
authors: Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10065, United States.
authors: Karina
authors: K
authors: Yazdanbakhsh
authors: Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10065, United States.
authors: Narla
authors: N
authors: Mohandas
authors: Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States.
authors: Henny H
authors: HH
authors: Billett
authors: Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10065, United States; Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, United States. Electronic address: pshi@nybloodcenter.org.
authors: Patricia A
authors: PA
authors: Shi
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D001596:Benzylamines; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000235:genetics; D000080027:Cyclams; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor
keywords: Endothelial cell activation; Hematopoietic progenitor cell mobilization; Neutrophil activation; Platelet activation; Plerixafor; Sickle cell disease