title: Dynamic roles of angiopoietin-like proteins 1, 2, 3, 4, 6 and 7 in the survival and enhancement of ex vivo expansion of bone-marrow hematopoietic stem cells.
abstract: Recent advances in hematopoietic stem cells (HSCs) expansion by growth factors including angiopoietin-like proteins (Angptls) have opened up the possibility to use HSCs in regenerative medicine. However, the unavailability of true in vitro HSCs expansion by these growth factors has limited the understanding of the cellular and molecular mechanism of HSCs expansion. Here, we report the functional role of mouse Angptls 1, 2, 3, 4, 6 and 7 and growth factors SCF, TPO, IGF-2 and FGF-1 on purified mouse bone-marrow (BM) Lineage(-)Sca-1(+)(Lin-Sca-1(+)) HSCs. The recombinant retroviral transduced-CHO-S cells that secrete Angptls in serum-free medium were used alone or in combination with growth factors (SCF, TPO, IGF-2 and FGF-1). None of the Angptls stimulated HSC proliferation, enhanced or inhibited HSCs colony formation, but they did support the survival of HSCs. By contrast, any of the six Angptls together with saturating levels of growth factors dramatically stimulated a 3- to 4.5-fold net expansion of HSCs compared to stimulation with a combination of those growth factors alone. These findings lead to an understanding of the basic function of Angptls on signaling pathways for the survival as well as expansion of HSCs in the bone marrow niche.
authors.affiliation: Department of Microbiology and Genetics and Institute for Medical Science, Chonbuk National University Medical School, Jeonju, 561-712, South Korea.
authors.forename: Shahina
authors.initials: S
authors.lastname: Akhter
authors.forename: Md Mashiar
authors.initials: MM
authors.lastname: Rahman
authors.forename: Hyun Seo
authors.initials: HS
authors.lastname: Lee
authors.forename: Hyeon-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Seong-Tshool
authors.initials: ST
authors.lastname: Hong
mesh_terms: D000091304:Angiopoietin-Like Protein 1; D000091302:Angiopoietin-Like Protein 2; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D014162:Transfection
chemical_list: D000091304:Angiopoietin-Like Protein 1; D000091302:Angiopoietin-Like Protein 2; D000091303:Angiopoietin-Like Protein 3; D000075803:Angiopoietin-Like Protein 4; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C529601:Angptl1 protein, mouse; C485793:Angptl2 protein, mouse; C404495:Angptl3 protein, mouse; C407088:Angptl4 protein, mouse; C477602:Angptl6 protein, mouse; D000950:Antigens, Ly; D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins