title: Role of SDF-1 (CXCL12) in regulating hematopoietic stem and progenitor cells traffic into the liver during extramedullary hematopoiesis induced by G-CSF, AMD3100 and PHZ.
abstract: The stromal cell derived factor 1 (SDF-1/CXCL12) plays an essential role in the homing of hematopoietic stem and progenitor cells (HSPCs) to bone marrow (BM). It is not known whether SDF-1 may also regulate the homing of HSPCs to the liver during extramedullary hematopoiesis (EMH). Here, we investigated the possible role of SDF-1 in attracting HSPCs to the liver during experimental EMH induced by the hematopoietic mobilizers G-CSF, AMD3100 and phenylhydrazine (PHZ). Mice treated with G-CSF, AMD3100 and PHZ showed a significant increase in the expression of SDF-1 in the liver sinusoidal endothelial cells (LSECs) microenvironments. Liver from mice treated with the hematopoietic mobilizers showed HSPCs located adjacent to the LSEC microenvironments, expressing high levels of SDF-1. An inverse relationship was found between the hepatic SDF-1 levels and those in the BM. In vitro, LSEC monolayers induced the migration of HSPCs, and this effect was significantly reduced by AMD3100. In conclusion, our results provide the first evidence showing that SDF-1 expressed by LSEC can be a major player in the recruitment of HSPCs to the liver during EMH induced by hematopoietic mobilizers.
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela.
authors.forename: Mayela
authors.initials: M
authors.lastname: Mendt
authors.affiliation: Unidad de Terapia Celular - Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela. Electronic address: jcardier@ivic.gob.ve.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Cardier
mesh_terms: D000818:Animals; D001596:Benzylamines; D001853:Bone Marrow / Q000737:chemistry / Q000502:physiology; D054377:Chemokine CXCL12 / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D000080027:Cyclams; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006411:Hematopoiesis, Extramedullary; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D010659:Phenylhydrazines / Q000494:pharmacology*
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D010659:Phenylhydrazines; C030299:phenylhydrazine; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor
keywords: AMD3100; Extramedullary hematopoiesis; G-CSF; Liver; SDF-1