title: Small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis.
abstract: Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into the blood circulation has been widely used for hematopoietic transplantation. However, the current methods of cytokine- or small-molecule-stimulated HSPC mobilization are far from satisfactory. New mobilizing agents are needed to increase the number of stem cells in peripheral blood for effective reconstitution of hematopoiesis. Here, we report that the molecule Me6TREN (Me6) can induce rapid mobilization of hematopoietic progenitor cells and that Me6 exhibits more significant effects than granulocyte colony-stimulating factor (G-CSF) or AMD3100. Me6 also mobilizes long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in primary and secondary transplant recipients. Mechanistically, Me6 inhibits both the SDF-1α-induced migration and VLA-4-mediated adhesion of mouse and human hematopoietic cells. Me6 appears to mobilize HSPCs by activating MMP-9 expression and disrupting the SDF-1α/CXCR4 axis. Therefore, Me6 may become a new potent and efficacious mobilizing agent of HSPCs.
authors.affiliation: Stem Cell and Regenerative Medicine Laboratory, Beijing Institute of Transfusion Medicine, Beijing, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Sihan
authors.initials: S
authors.lastname: Wang
authors.forename: Haixu
authors.initials: H
authors.lastname: Chen
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Lv
authors.forename: Junnian
authors.initials: J
authors.lastname: Zhou
authors.forename: Xue
authors.initials: X
authors.lastname: Nan
authors.forename: Lijuan
authors.initials: L
authors.lastname: He
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Xuetao
authors.initials: X
authors.lastname: Pei
mesh_terms: D000818:Animals; D001596:Benzylamines; D002448:Cell Adhesion; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D005021:Ethylamines / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4 / Q000378:metabolism; D013997:Time Factors
chemical_list: D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D000080027:Cyclams; D005021:Ethylamines; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C587015:tris(2-(dimethylamino)ethyl)amine; D016179:Granulocyte Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9; C088327:plerixafor