The architecture of bone marrow cell populations

Abstract

Marrow is a loosely bound tissue in which hemopoiesis has frequently been considered to be randomly distributed. The case is presented, however, for an organized and structured marrow in which close relationships exist between hemopoietic tissue and a regulatory microenvironment. Distributions of myeloid cells in the mouse femur are described, and a dynamic picture of their movement, with differentiation and maturation from the endosteal surface of the bone to their release via the central venous sinus, is painted. It is also shown that this structure is established within three weeks of birth. By contrast, mature lymphoid cells (but not their progenitors) are uniformly distributed. Regulatory stromal elements in the marrow are also structured and their localization is found to correspond closely to the properties of the progenitor populations. Such structure has potential practical importance, particularly in the field of medical, industrial or accidental radiation exposure where bone may introduce non-uniform dose distributions in the marrow.

The expansion of murine bone marrow cells preincubated in hypoxia as an in vitro indicator of their marrow-repopulating ability

“…In hypoxia, in other words, STR progenitors would be able to remain in a quiescent state, yet being recruitable to commitment and clonal expansion. 10,11 On this basis, the 5FU experiments reported here provide experimental support to our hypothesis that, in relatively hypoxic areas of BM, the progenitors' response to recruitment/proliferation/differentiation stimuli is modulated in favor of their maintenance and long-term conservation. 1 To generate lineage-restricted progeny and then undergo extensive clonal expansion, STR progenitors would be required to move to areas of BM at higher oxygen tensions, a process mimicked in our experimental system by culture transfer to air.…”

Targeting the stem cell niche: squeezing blood from bones

“…Mammalian bone marrow involves HSCs close to the endosteal surfaces, with the more differentiated cells closer to the central axis of the bone. 6 This organized structure of the marrow suggests a relationship between HSCs and osteoblasts and osteogenic cells lining the endosteal surface. Osteoblasts produce hematopoietic growth factors and are activated by parathyroid hormone (PTH) or the locally produced, PTH-related protein, through the PTH/PTHrP receptor (PRP).…”

Osteoblastic cells regulate the haematopoietic stem cell niche

“…Therefore, osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation. Niche constituent cells or signalling pathways provide pharmacological targets with therapeutic potential for stem-cell-based therapies.Mammalian bone marrow architecture involves haematopoietic stem cells (HSCs) in close proximity to the endosteal surfaces 5,6 , with more differentiated cells arranged in a loosely graduated fashion as the central longitudinal axis of the bone is approached 5,7,8 . This nonrandom organization of the marrow suggests a possible relationship between HSCs and osteoblasts-osteogenic cells lining the endosteal surface.…”

“…Mammalian bone marrow architecture involves haematopoietic stem cells (HSCs) in close proximity to the endosteal surfaces 5,6 , with more differentiated cells arranged in a loosely graduated fashion as the central longitudinal axis of the bone is approached 5,7,8 . This nonrandom organization of the marrow suggests a possible relationship between HSCs and osteoblasts-osteogenic cells lining the endosteal surface.…”

“…We investigate here the role of pathway activity in tumours derived from the gut, a tissue with prominent and diverse roles for Hh signalling in developmental patterning, and in mature tissue homeostasis. A role in homeostasis is suggested by the expression of Hh ligands and target genes in postnatal gut epithelium and mesenchyme [8][9][10][11] (Fig. 1a).…”