Evidence for a continuous decline in haemopoietic cell function from birth: application to evaluating bone marrow failure in children

Abstract

There are considerable differences in haemopoietic activity between young children and adults on the one hand, and between adults and the elderly on the other. A fundamental unanswered question is whether these differences relate to discrete stages or are part of a continuous process. We have sought to define aspects of the haematological ageing process, and have found that results from children with bone marrow failure syndromes differ from age-matched reference values. Haemopoietic cells were obtained from umbilical cord blood, from blood and bone marrow of healthy individuals and from the blood of young patients with bone marrow failure syndromes. Clonogenic myeloid progenitors (CFU-GM) were grown in semi-solid medium to measure their frequency; the proliferative capacity of myeloid progenitors was measured by replating colonies and observing secondary colony formation. We found that the frequency of CFU-GM in normal marrow increased and their proliferative capacity decreased exponentially with age. The proliferative capacity of CFU-GM in normal blood also decreased exponentially with age. This relationship extrapolated back to the levels of proliferation measured for cord blood CFU-GM (age = 0). The proliferative capacities of CFU-GM from children with bone marrow failure syndromes were severely reduced compared with age-matched reference values. These results indicate that a decline in haemopoietic progenitor cell function begins at birth and continues throughout life. This decline may occur prematurely in childhood marrow failure syndromes with a predisposition to leukaemia.

Modeling the Prostate Stem Cell Niche: An Evaluation of Stem Cell Survival and Expansion In Vitro

“…Wilson et al [8] showed that dormant HSCs are not just resting but deeply inactive as they have reduced metabolism, ribosomal biogenesis, and DNA replication. There is further evidence for a continuous decline in stem cell function from birth [40]. The mechanism for this was recently described as the misorientation of centrosomes with age, leading to a reduction in the correct establishment of asymmetric stem cell division with respect to its niche [41].…”

Early hematopoiesis inhibition under chronic radiation exposure in humans

“…Progenitor cell pool which plays the role of a pluripotent precursor reserve decreases with age (Bagnara et al 2000). The ability of the progenitor pool to self-maintenance diminishes too (Marley et al 1999). Chronic radiation exposure as a stress factor can lead to different degrees of hematopoietic insufficiency manifested by elderly people.…”

The GOD of Hematopoietic Stem Cells: A Clonal Diversity Model of the Stem Cell Compartment

“…However, changes in the HSC compartment can be induced-for example through diseases, chemotherapy, transplantation, cytokine treatment, and aging. 43,34,[44][45][46][47][48][49][50][51][52][53] After such events the HSC compartment can become pauciclonal.…”