%0 Journal Article
%T Mesenchymal Stem Cells in Immune-Mediated Bone Marrow Failure Syndromes
%A Maria-Christina Kastrinaki
%A Konstantia Pavlaki
%A Aristea K. Batsali
%A Elisavet Kouvidi
%A Irene Mavroudi
%A Charalampos Pontikoglou
%A Helen A. Papadaki
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/265608
%X Immune-mediated bone marrow failure syndromes (BMFS) are characterized by ineffective marrow haemopoiesis and subsequent peripheral cytopenias. Ineffective haemopoiesis is the result of a complex marrow deregulation including genetic, epigenetic, and immune-mediated alterations in haemopoietic stem/progenitor cells, as well as abnormal haemopoietic-to-stromal cell interactions, with abnormal release of haemopoietic growth factors, chemokines, and inhibitors. Mesenchymal stem/stromal cells (MSCs) and their progeny (i.e., osteoblasts, adipocytes, and reticular cells) are considered as key cellular components of the bone marrow haemopoietic niche. MSCs may interfere with haemopoietic as well as immune regulation. Evidence suggests that bone marrow MSCs may be involved in immune-mediated BMFS underlying pathophysiology, harboring either native abnormalities and/or secondary defects, caused by exposure to activated marrow components. This review summarizes previous as well as more recent information related to the biologic/functional characteristics of bone marrow MSCs in myelodysplastic syndromes, acquired aplastic anemia, and chronic idiopathic neutropenia. 1. Introduction Immune-mediated bone marrow failure syndromes (BMFS), such as the myelodysplastic syndromes, acquired aplastic anemia, or chronic idiopathic neutropenia, are characterized by ineffective marrow haemopoiesis and subsequent peripheral cytopenias. Pathogenetic mechanisms involve a complex marrow deregulation, including genetic and epigenetic alterations, resulting in aberrant release of haemopoietic growth factors and inhibitors in the marrow, deregulated immune manifestations, all resulting in defective haemopoietic maturation and increased haemopoietic cell apoptosis. Normal haemopoiesis is regulated in the marrow by an extended network of specialized niches, maintaining haemopoietic stem cell (HSC) self-renewal and orchestrating HSC proliferation and differentiation to all blood cell types. Key cellular components of the bone marrow (BM) haemopoietic microenvironment include osteoblasts, sinusoidal endothelial cells, macrophages, adipocytes, and reticular cells, orchestrating the maintenance, proliferation, and differentiation of haemopoietic stem and progenitor cells (HSPCs). Osteoblasts, adipocytes, and reticular cells of the marrow stroma derive from a common progenitor cell, the mesenchymal stem/stromal cell (MSC) [1¨C5]. Since MSCs and their progeny are among the main components of the marrow stroma, it is reasonable to assume that patient BM MSCs may be partially defective,
%U http://www.hindawi.com/journals/jir/2013/265608/