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Indian Journal of Medical and Paediatric Oncology
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Year : 2003  |  Volume : 24  |  Issue : 4  |  Page : 6-12

Flt-3 ligand increases the effect of cytokines on CFU-GM colony formation from human cord blood and fetal liver CD34 plus cells

Department of Pediatrics Research Center of Michigan

Correspondence Address:
S Bakhshi
Department of Pediatrics Research Center of Michigan

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Source of Support: None, Conflict of Interest: None

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Background: Transplantation of primary isolates of human cord blood (CB) and fetal liver (FL) hematopoietic stem cells, and the use of ex vivo expanded progenitor cells from these sources hold promise for the treatment of a number of diseases. In order to fully realize the potential of this method and these cells, an understanding of the expression of hematopoietic growth factor receptors and the function of their ligands is crucial. Flt3 receptor is a member of the tyrosine kinase receptor familyand its ligand is a cytokine involved in hematopoiesis, and may have a significant potential for the expansion of hematopoietic stem cells ex vivo. Methods: We investigated the expression of flt3 receptor in CD34plus cells from CB and FL using RT-PCR andflow-cytometry. We also studied the colony forming potential of CB and FL CD34plus cells in methylcellulose culture using a combination of cytokines that included SCF, IL-3, IL-6, GM-CSF, G-CSF and erythropoietin with and without flt3 ligand. Results: Flt3 receptor mRNA and protein expression were observed in CD34plus cells from CB and FL. After 14 days in methylcellulose culture, there was a statistically significant increase in the number of CFU-GM but not BFU-E or CFU-GEMM colonies, when flt3 ligand was added to the cytokine cocktail. The increase in CFU-GM with flt3 ligand was reduced when anti-flt3 ligand antibody was added to the culture. Conclusions: These observations suggest that flt3 ligand may play a synergistic role with cytokines in augmenting CFU-GM formation from both CB and FL CD34plus cells.

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