Effect of Age on the Frequency, Cell Cycle, and Lineage Maturation of Rhesus Monkey (Macaca mulatta) CD34+ and Hematopoietic Progenitor Cells

Abstract

The effects of maturation and aging on hematopoietic progenitor cells, blood and bone marrow from second- and third-trimester fetal, newborn, infant, adult, and aged rhesus monkeys (Macaca mulatta) were analyzed. CD34⁺ cells were immunoselected and stained with propidium iodide for cell cycle analysis. Blood and bone marrow mononuclear cells were plated in methylcellulose, and erythroid and myeloid progenitors were grown and counted. A higher frequency of circulating CD34⁺CD38⁻ and CD34⁺DR⁻ cells was observed in second-trimester fetuses compared with the other age groups. The frequency of bone marrow CD34⁺CD38⁻ and CD34⁺DR⁻ cells declined in adult and aged animals when compared with the younger age groups. Cell-cycle analysis showed 4.5% second-trimester fetal bone marrow CD34⁺ cells entering the G₂/M phase, compared with 1.7% CD34⁺ cells in aged animals. More than 95% of circulating CD34⁺ cells remained quiescent for most age groups, except for second-trimester fetuses. Adult marrow myeloid progenitors were found in a lower quantity when compared with third-trimester fetuses, whereas erythroid progenitors were greatest in early-gestation fetuses and adults. The results of these studies suggest that 1) the greatest quantity of CD34⁺CD38⁻ and CD34⁺DR⁻ cells was found in fetal and infant bone marrow, 2) the frequency of cycling CD34⁺ cells declines with maturation and aging, and 3) an age-dependent difference in lineage commitment occurs.