The in vitro effects of stem cell factor and PIXY321 on myeloid progenitor formation (CFU-GM) from immunomagnetic separated CD34+ cord blood.
Two novel cytokines, stem cell factor (SCF) and PIXY321 (a fusion protein, granulocyte macrophage colony-stimulating factor+IL-3), have recently been demonstrated to enhance in vitro adult myelopoiesis. In this study, we compared the success of separating very early hematopoietic progenitor cells (CD34+) from both cord blood (CB) and adult bone marrow (ABM) and their differential response to SCF, PIXY321, and other later-acting colony-stimulating factors (CSF). Briefly, CD34+ cells were isolated from CB and ABM with an anti-CD34 MAb, HPCA-1, and incubated with various combinations of SCF, PIXY321, and other CSF. The percentage of CD34+ cells was decreased in CB compared to ABM before separation (0.54 versus 1.71%) (p = 0.05). Isolated CD34+ cells from CB and ABM were similar in lineage with respect to CD38, HLA-DR, CD33, and CD5, but decreased in CB with respect to B-lineage expression (CD19, CD10, and CD22) (p = 0.05). SCF increased colony forming unit-granulocyte-macrophage (CFU-GM) formation from CB CD34+ cells compared to unconditioned media and had a significant additive increase with IL-3 (p = 0.006) and granulocyte colony-stimulating factor (p = 0.03). SCF also had an additive increase in CB CFU-GM formation with PIXY321 (p = 0.007). PIXY321 had a similar increase in CFU-GM formation from both CB and ABM CD34+ cells compared to the combination granulocyte macrophage colony-stimulating factor + IL-3. When SCF was added to IL-3, PIXY321, or PIXY321 + IL-6, there was an increase in CFU-GM from CB versus ABM CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Cairo
M S
MS
Division of Hematology/Oncology, Children's Hospital of Orange County, California 92668.
Law
P
P
van de Ven
C
C
Plunkett
J M
JM
Williams
D
D
Ishizawa
L
L
Gee
A
A
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D005312:Fetal Blood / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000737:chemistry*; D006801:Humans; D007231:Infant, Newborn; D019089:Stem Cell Factor
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor