Retinoic acid receptor antagonist inhibits CD38 antigen expression on human hematopoietic cells in vitro.
The CD34+ CD38- subset of human hematopoietic stem cells are crucial for long-term ex-vivo expansion; conditions that decreased this specific sub-population reduced the self-renewal capacity and shortened the duration of the proliferative phase of the culture. Retinoids, such as all-trans retinoic acid (ATRA), have been shown to induce CD38 expression. ATRA present in serum may be responsible for the high CD38 of cells grown in serum-containing medium. In the present study we analyzed the effects of AGN 194310, a retinoic acid receptor pan-antagonist, on CD38 expression of human hematopoietic cells. Normal cells (cord blood derived CD34+ cells) and abnormal cells (myeloid leukemic lines) were studied when grown in either serum-containing or serum-free media. The results showed that both serum and ATRA enhanced differentiation and, thereby, reduced the proportion of CD34+ CD38- cells and total CD34+ cell expansion. AGN reversed these effects of serum and ATRA: it delayed differentiation and increased CD34+ CD38- cells. These results suggest that physiological ATRA levels in serum may prevent efficient cell expansion. AGN, by neutralizing ATRA, improves cell expansion in serum-containing cultures, thus making AGN a useful agent for ex vivo expansion of stem cells and other specific sub-populations for research and clinical use.
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Eugenia
E
Prus
Roshantha A S
RA
Chandraratna
Eitan
E
Fibach
D036541:ADP-ribosyl Cyclase / Q000187:drug effects* / Q000235:genetics; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000187:drug effects* / Q000235:genetics; D018952:Antigens, CD34; D001565:Benzoates / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D004347:Drug Interactions; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000494:pharmacology
C121616:4-((4-(4-ethylphenyl)-2,2-dimethyl-(2H)-thiochromen-6-yl)ethynyl)benzoic acid; D015703:Antigens, CD; D018952:Antigens, CD34; D001565:Benzoates; D008562:Membrane Glycoproteins; D018168:Receptors, Retinoic Acid; D013876:Thiophenes; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1