الفهرس 
Chapter 1. The concept of the nicheOnly 14 pages are availabe for public view
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Abstract
Stem cell niches are present wherever stem cells are. Hematopoietic stem cells (HSCs) that produce a variety of hematopoietic lineage cells throughout the life reside in specialized microenvironment called “niche” in the bone marrow (BM) where they are tightly regulated.
Recent advances in defining different mesenchymal and endothelial bone marrow cell populations greatly enhanced our understanding of these niches and of the molecular mechanisms by which they regulate and support HSCs function and maintain a correct balance between self-renewal and differentiation.
This review provides a brief summary of the current knowledge on the BM microenvironment and its associated elements, as well as of the molecular networks that regulate or influence hematopoiesis in health and disease.
Bone marrow endothelial cells are known to release cytokines, signaling mediators, and growth factors into the BM microenvironment. They have been shown to support HSC maintenance by providing factors, such as, CXCL12, SCF, angiopoietin, fibroblast growth factor (FGF) 2, and Delta-like 1; therefore, regulating HSC quiescence, expansion, and activation.
Mesenchymal stromal cells (MSCs) are a heterogeneous self-renewing population of cells defined by a set of different markers, such as nestin, neural-glial antigen (NG)-2, leptin receptor or paired related homeobox (Prx-1) and are enriched close to the vasculature in the BM microenvironment. MSCs give rise to different lineages, including osteoblastic cells, chondrocytes and adipocytes. Different progeny of MSCs associate with HSCs and, in general, most of them are known to secrete HSC-supporting factors, such as C-X-C motif chemokine ligand 12 (CXCL12), angiopoietin, stem cell factor (SCF/Kit ligand) and others, but differences according to MSC type and location, i.e. arteriolar or sinusoidal, have been revealed .
The endosteum lies at the interface between bone and bone marrow and is predominantly composed of osteoblastic cells, which can also regulate the number and function of HSCs.Furthermore, bone-degrading osteoclasts and osteocytes also affect hematopoiesis. The nervous system also plays a role in the BM niche, as neuroglial cells regulate HSCs traffic and proliferation. Mature hematopoietic cells and cells from the immune system (megakaryocytes, macrophages, and T cells) also play distinct supportive functions for HSCs in the BM niche.
In addition to the role in maintaining HSCs homeostasis, the niche has also been implicated in the pathogenesis of hematological malignant and nonmalignant disorders.
Deregulation of HSCs activity within the BM niche is a key factor in the development of hematological malignancies as myelodysplasia, multiple myeloma and acute myeloid leukemia. Understanding bone marrow microenvironment could change how myelodysplastic syndromes are diagnosed and treated. Recent findings indicate that leukemic cells (myeloid malignancies in particular) affect the function of BM niche components and vice versa, pointing toward the existence of an active cross talk between the two compartments. Multiple myeloma and other cancer cells hijack and alter the bone marrow niche and are altered by the niche in turn; thus, targeting niche–cancer interactions is a promising therapeutic avenue.
Niche dysregulation can result also in nonmalignant hematologic disorders as aplastic anemia, idiopathic thrombocytopenia and paroxysmal nocturnal hemoglobinuria.
Owing to these complexities, a comprehensive understanding of the interactions between HSCs and the BM microenvironment and how these interactions are altered in pathological states can aid the design of therapeutic strategies.