Errata
Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment
(1) Hematopoietic microenvironment cells advance along a three stage differentiation/maturation pathway. In the first stage, they support hematopoiesis and contain no fat. In the second stage, cells accumulate fat and no longer support steady state hematopoiesis; however, under conditions of increased hematopoietic requirement, they lose fat and regain their ability to support hematopoiesis. In the last stage, hematopoietic microenvironment cells retain the appearance of yellow bone marrow and do not support hematopoiesis regardless of the state of hematopoietic requirement.
(2) Since MSCs are bound to endosteal and trabecular surfaces, in tubular bones their number is relatively small, compared to cancellous bones that have much larger areas of internal bone surface. MSCs are exposed to proliferative and differentiative pressures, leading to gradual reduction of their number. Consequently, the MSC population in tubular bones becomes exhausted rather early, and the post-maturation compartment of mesenchymal cells finally consists of unipotential bone precursors maintaining bone tissue and hematopoietic microenvironment advancing towards the last (fatty) stage of differentiation. In contrast, in cancellous bones the relatively large number of MSCs does not suffer exhaustion and continues to provide newly differentiated hematopoietic microenvironment, thus maintaining red bone marrow throughout the organism’s life.
(3) Osteogenic and hematopoietic microenvironment differentiation pathways compete with each other for their common precursor. During the organism’s growth period osteogenic stimuli prevail, while in the post-maturation period, MSC differentiation into hematopoietic microenvironment increases at the expense of differentiation into bone. This results in the reduction of bone volume and expansion of marrow cavities in hematopoietically active cancellous bones, but not in tubular bones already depleted of MSCs and not participating in hematopoiesis.
Experimental and clinical data supporting these hypotheses are discussed.
float:right; padding-left:5px">foBubble.hide()"> Blood Cells, Molecules, and Diseases, Volume 21, Issue 2, August 1995, Pages 73-85 Lorenza Caneva, Davide Soligo, Giorgio Cattoretti, Etienne De Harven, Giorgio Lambertenghi Deliliers Abstract ABSTRACT Human bone marrow stromal cells have been examined with an immuno-electron microscopy technique in order to better define their structure and function in normal hematopoiesis. Bone marrow fragments from normal donors, after mild permeabilization and glutaraldehyde prefixation were labeled with the Me20.4 Mab, which recognizes the low-affinity nerve growth factor (NGFR) and was recently described as specifically identifying fibroblastic-like bone marrow stromal cells. Five nm gold immuno-conjugates served as markers. NGFR+ cells were showing either a star-shape, with long and convoluted dendritic projections, and branching with each other to form a complex system of lacunae upon which hematopoietic cells were arranged. Other NGFR+ cells had an elongated spindle-like morphology. NGFR+ dendrites were seen in close contact with each other and with the different hematopoietic cells, although definite junctions were never noticed. NGFR+ dendrites were also observed surrounding mature plasma cells, in close apposition with adipocytes or surrounding bone marrow sinusoids. These findings may give some clues about the function of the bone marrow stromal cells, which are known to be involved in the homing and recirculation of hemopoietic cells; in addition, the presence and distribution of NGFR in the bone marrow stroma may support the recent evidence of a co-stimulatory effect of NGF in early hematopoiesis. f="http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBV-45N4NRX-B-1&_cdi=6720&_user=10&_orig=article&_coverDate=08%2F31%2F1995&_sk=999789997&view=c&wchp=dGLzVzz-zSkWW&md5=0019fe40e70af2c2c1fa603c2ac19950&ie=/sdarticle.pdf"> |
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Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment