IL-11 in combination with SLF and G-CSF or GM-CSF significantly increases expansion of isolated CD34+ cell population from cord blood vs. adult bone marrow.
Hematopoietic progenitor cells in human umbilical cord blood have been shown to be effective sources for hematopoietic reconstitution following myeloablative therapy. Unfortunately, the use of cord blood (CB) is limited by the number of progenitor cells necessary to reconstitute the older child or adult. We studied the expansion of an isolated population of CD34+ cells from CB and adult bone marrow (ABM) after 1 to 3 weeks in culture when stimulated with lineage-nonspecific (IL-11 and/or SLF) and lineage-specific (G-CSF or GM-CSF) cytokines. IL-11 and SLF alone or in combination did not enhance expansion of CB CD34+ stem cells. With combinations of IL-11, SLF, and G-CSF or GM-CSF, however, after 1, 2, or 3 weeks in culture, WBC expansion was significantly greater in CB vs. ABM (p < 0.05). At all time points, expanded CB consistently demonstrated a significant increase in cell production and myeloid differentiation when compared to ABM. To assess the proliferative potential of the expanded cultures, cells were recovered from the expansion cultures, plated in methylcellulose, and evaluated for CFU-GM and CFU-Meg colony formation. After 2 weeks in culture, a significant increase in CFU-GM colony formation in CB vs. ABM was demonstrated with SLF (p < 0.001), IL-11 plus SLF (p < 0.0005), and IL-11 plus SLF plus G-CSF (p < 0.004). Significantly greater CFU-Meg formation was also seen in CB vs. ABM cells plated after expansion with IL-11 plus SLF plus G-CSF (weeks 1 and 2) or IL-11 plus SLF plus GM-CSF (week 1) (p < 0.05). Finally, immunophenotyping was performed on CB cultures on days 0 and 14, and although a significant reduction of the percentage of progenitors (CD34+/38+/38-/DR+) was seen, their absolute numbers were maintained. (Data for ABM was not available). This study suggests that IL-11, when combined with SLF and more lineage-specific cytokines, can effectively maintain primitive multipotential progenitors and stimulate the differentiation of more committed precursors in CB compared to ABM.
van de Ven
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C
Division of Hematology/Oncology, Children's Hospital of Orange County, Orange, CA 92668, USA.
Ishizawa
L
L
Law
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P
Cairo
M S
MS
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D017370:Interleukin-11 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology*
D018952:Antigens, CD34; D017370:Interleukin-11; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor