Abstract
To evaluate the effect of all-trans retinoic acid (RA) on fetal haemopoiesis, we performed serum-free liquid and semisolid cultures using CD34+ cells purified from midtrimester human fetal blood samples. RA, at both physiological (10(-11) and 10(-12)M) and pharmacological (10(-6) and 10(-7)M) concentrations, significantly (P < 0.01) promoted the survival of fetal CD34+ cells in liquid cultures from day 3 onwards, by suppressing apoptosis induced by serum and growth factor deprivation. On the other hand, RA alone had no significant effect on the proliferation and differentiation of fetal haemopoietic progenitors. In the presence of optimal concentrations of recombinant interleukin-3 (IL-3), stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), and erythropoietin (Epo), low and high doses of RA induced striking differential effects on CD34+ cell proliferation in liquid cultures and colony formation in semisolid assays. In fact, 10(-11)M and 10(-12)M RA were able to: (i) significantly (P < 0.05) increase 3H-thymidine uptake by fetal CD34+ cells in liquid cultures, and (ii) variably promote the growth of pluripotent (CFU-GEMM, P < 0.05), early (BFU-meg) and late (CFU-meg, P < 0.01) megakaryocyte, granul...Continue Reading
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