Stem cells in the bone marrow compartment

Less than 0.1% of all nucleated cells in the bone marrow are stem cells. Among these, hematopoietic stem cells (HSCs) provide a source of circulating erythrocytes, leukocytes, and platelets (Fig. 1). The HSC pool can be subdivided into long-term reconstituting HSCs, which have the greatest self-renewal capacity, and short-term HSCs, which generate hematopoietic lineages only for several weeks (11). Mesenchymal (stromal) stem cells

From: Adult Stem Cells Edited by: K. Turksen © Humana Press Inc., Totowa, NJ

Fig. 1. Schematic view of the bone marrow stem cell compartments. Hematopoietic stem cells (HSCs) and mesenchymal (stromal) stem cells (MSCs) become gradually restricted in their differentiation potential by a succession of cell divisions. Common lymphoid progenitors (CLP) arise from HSCs and differentiate into T lymphocytes (TL) and B lymphocytes (BL). Common multipotent progenitors (CMP) derive from HSCs and give rise to monocytes/macrophages (Mac), neutro-phil granulocytes (Gr), eosinophil granulocytes (Eos), erythroblasts/erythrocytes (E), and megakaryocytes/platelets (P). MSCs generate progenitor cells, which differentiate into hematopoietic-supporting stroma (S), adipocytes (A), tenocytes (T), chondrocytes (C), and osteocytes (O). Endothelial progenitor cells (EPCs) can be mobilized into the blood and give rise to vascular endothelial cells (En).

Fig. 1. Schematic view of the bone marrow stem cell compartments. Hematopoietic stem cells (HSCs) and mesenchymal (stromal) stem cells (MSCs) become gradually restricted in their differentiation potential by a succession of cell divisions. Common lymphoid progenitors (CLP) arise from HSCs and differentiate into T lymphocytes (TL) and B lymphocytes (BL). Common multipotent progenitors (CMP) derive from HSCs and give rise to monocytes/macrophages (Mac), neutro-phil granulocytes (Gr), eosinophil granulocytes (Eos), erythroblasts/erythrocytes (E), and megakaryocytes/platelets (P). MSCs generate progenitor cells, which differentiate into hematopoietic-supporting stroma (S), adipocytes (A), tenocytes (T), chondrocytes (C), and osteocytes (O). Endothelial progenitor cells (EPCs) can be mobilized into the blood and give rise to vascular endothelial cells (En).

(MSCs) generate nonhematopoietic tissues, including adipocytes, tenocytes, hematopoietic-supporting stroma, chondrocytes, and osteocytes (Fig. 1) (12). The bone marrow cavity also contains endothelial progenitor cells (EPCs), which can be mobilized into the peripheral blood and give rise to mature endothelial cells in vessels (Fig. 1) (13).

All bone marrow stem cells derive from mesoderm, but it is unclear at present how HSCs arise and what their relationship to endothelial cells is (14). Unfortunately, cell surface determinants provide only limited information on the origin of particular stem cells, and even highly enriched bone marrow stem cell populations remain heterogeneous. This has to be taken into account when plasticity is attributed specifically to HSCs or MSCs.

The expression of CD34/Stem cell antigen 1 (Sca-1), c-Kit, and CD45 antigens in the absence of lineage markers helps to differentiate HSCs from MSCs. Nevertheless, some HSCs are also found in the CD34- fraction (15). HSCs also express the ABC transporter Bcrpl, which effluxes dyes such as Hoechst-33342 and allows the selection of the so-called side population of HSCs (16,17). MSCs can be enriched in vitro based on their adhesive properties and the presence of CD44 (18). Finally, EPCs express CD34/Sca-1, vascular endothelial growth factor receptor2 (Flk-1), and Tie-2 antigens (13). They can be mobilized into the circulation by granulocyte-macrophage colony-stimulating factor, vascular endothelial growth factor, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (19-21). Selected by adherence to plastic, some of the EPCs may be of hema-topoietic origin given that monocytes have been shown to give rise to endot-helial-like cells in vitro (22).

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