Differentiation of hematopoietic progenitor cells towards the myeloid and B-lymphoid lineage by hepatocyte growth factor (HGF) and thrombopoietin (TPO) together with early acting cytokines

Autor: Reinhard Andreesen, Leoni A. Kunz-Schughart, Burkhard Hennemann, Matthias Zaiss, Jochen Grassinger, Gunnar Mueller
Rok vydání: 2006
Předmět:
Myeloid
Cellular differentiation
Transplantation
Heterologous
610 Medizin
Mice
SCID
Biology
CD34
differentiation
hematopoietic progenitor cells
hepatocyte growth factor
thrombopoietin
lymphopoiesis
Colony-Forming Units Assay
Mice
Mice
Inbred NOD
medicine
Animals
Humans
Cell Lineage
Myeloid Cells
Lymphopoiesis
Progenitor cell
Cells
Cultured
Interleukin 3
B-Lymphocytes
Stem Cell Factor
Dose-Response Relationship
Drug
Hepatocyte Growth Factor
Interleukin-6
Hematopoietic Stem Cell Transplantation
Membrane Proteins
Cell Differentiation
Drug Synergism
Hematology
General Medicine
Hematopoietic Stem Cells
Molecular biology
Recombinant Proteins
Endothelial stem cell
Haematopoiesis
medicine.anatomical_structure
Thrombopoietin
Radiation Chimera
Immunology
Hepatocyte growth factor
Granulocytes
medicine.drug
Zdroj: European Journal of Haematology. 77:134-144
ISSN: 1600-0609
0902-4441
Popis: Objectives: The effect of stem cell factor (SCF), flt3-ligand (FL), and interleukin (IL)-3 (SF3) in combination with hepatocyte growth factor (HGF), thrombopoietin (TPO), and Hyper-IL-6 on maintenance and differentiation of early human peripheral blood-derived progenitor cells was investigated. Methods: Single sorted CD34(+) 38(-) cells were cultured with various combinations of these growth factors in order to identify the most effective cytokine combination. Then, lineage-depleted cells were stimulated for 7 d in bulk culture before they were assessed by flow cytometry and in functional assays. Results: The highest number of clones in the single-cell assay was obtained after culture with SF3 + TPO + HGF. Cell expansion with SF3 + TPO + HGF yielded an increase of the total cell number (11-fold), the number of CD34(+) cells (sevenfold), colony forming cells (CFC; 13-fold), granulocytes (CD15/66b(+); 45-fold) and B-cells (CD19/20(+); 55-fold). However, the number of long-term culture initiating cells (LTC-IC) decreased from 779 +/- 338 per 1 x 10(5) CD34(+) cells on day 0 to 253 +/- 115 on day 7. In parallel, the number of pluripotent mouse repopulating cells decreased by the factor 11, and no significant change in the proportion of human myeloid or lymphoid cells found in the mouse bone marrow was noted. Conclusion: The observation that mature cells of different lineages are generated and that transplantable multipotent hematopoietic cells are lost during culture suggests the differentiation of early hematopoietic progenitors toward lineage committed cells by the tested cytokines. The detection of cells expressing B-lymphoid markers after culture indicates a possible role in the propagation of B-cells.
Databáze: OpenAIRE
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