Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein-1 alpha.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97463
Title:
Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein-1 alpha.
Authors:
Lord, Brian I; Woolford, Lorna B; Wood, L M; Czaplewski, Lloyd G; McCourt, M; Hunter, Michael G; Edwards, R Mark
Abstract:
BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G-CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100-fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB-10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.
Affiliation:
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK.
Citation:
Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein-1 alpha. 1995, 85 (12):3412-5 Blood
Journal:
Blood
Issue Date:
15-Jun-1995
URI:
http://hdl.handle.net/10541/97463
PubMed ID:
7540061
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLord, Brian Ien
dc.contributor.authorWoolford, Lorna Ben
dc.contributor.authorWood, L Men
dc.contributor.authorCzaplewski, Lloyd Gen
dc.contributor.authorMcCourt, Men
dc.contributor.authorHunter, Michael Gen
dc.contributor.authorEdwards, R Marken
dc.date.accessioned2010-04-27T14:24:58Z-
dc.date.available2010-04-27T14:24:58Z-
dc.date.issued1995-06-15-
dc.identifier.citationMobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein-1 alpha. 1995, 85 (12):3412-5 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid7540061-
dc.identifier.urihttp://hdl.handle.net/10541/97463-
dc.description.abstractBB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G-CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100-fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB-10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshCell Count-
dc.subject.meshChemokine CCL3-
dc.subject.meshChemokine CCL4-
dc.subject.meshColony-Forming Units Assay-
dc.subject.meshCytokines-
dc.subject.meshGranulocyte Colony-Stimulating Factor-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshMacrophage Inflammatory Proteins-
dc.subject.meshMice-
dc.subject.meshMonokines-
dc.subject.meshRecombinant Proteins-
dc.titleMobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein-1 alpha.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK.en
dc.identifier.journalBlooden

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