Bone Marrow Mesenchymal Stem Cells: Biological Properties and Their Role in Hematopoiesis and Hematopoietic Stem Cell Transplantation

Abstract

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are present in practically all tissues as a specialized population of mural cells/pericytes that lie on the abluminal side of blood vessels. Originally identified within the bone marrow (BM) stroma, not only do they provide microenvironmental support for hematopoietic stem cells (HSCs), but can also differentiate into various mesodermal lineages. MSCs can easily be isolated from the BM and subsequently expand in vitro and in addition they exhibit intriguing immunomodulatory properties, thereby emerging as attractive candidates for various therapeutic applications. This review addresses the concept of BM MSCs via a hematologist's point of view. In this context it discusses the stem cell properties that have been attributed to BM MSCs, as compared to those of the prototypic hematopoietic stem cell model and then gives a brief overview of the in vitro and vivo features of the former, emphasizing on their immunoregulatory properties and their hematopoiesis-supporting role. In addition, the qualitative and quantitative characteristics of BM MSCs within the context of a defective microenvironment, such as the one characterizing Myelodysplastic Syndromes are described and the potential involvement of these cells in the pathophysiology of the disease is discussed. Finally, emerging clinical applications of BM MSCs in the field of hematopoietic stem cell transplantation are reviewed and potential hazards from MSC use are outlined.

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…While most of our understanding of MSCs is based on ex vivo cultured cells, their in vivo counterparts, along with their origin, localisation, potential and roles in disease have remained elusive (Pontikoglou et al, 2011).…”

“…In order to isolate a pure MSC population, several new markers have been suggested to further define MSC. These markers include Stro-1, GD2, SSEA4, CD49a, CD146, CD200, CD271, Sca1, CD24, CD140a (PDGFRα) and CD140b (PDGFRβ) (Pontikoglou et al, 2011). As well as using these markers to define MSC as a whole, these will also be essential in understanding how this heterogeneous population may be subdivided into discrete groups which fulfil specific roles.…”

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

“…The nonhematopoietic components of the BM microenvironment are thought to derive from MSCs [15][16][17]. This population has been shown to support hematopoiesis [15] and to affect B-cell proliferation and differentiation either positively or negatively [18,19], thereby providing the theoretical background for studying the MSC putative role in CLL pathogenesis. Notably, this particular field of research has not been extensively explored.…”

“…The BM microenvironment consists of a heterogeneous population of cells, of both mesenchymal and hematopoietic origin, which produce the extracellular matrix and soluble factors and also provide the cellular surface, collectively regulating the growth, proliferation, and differentiation of hematopoietic stem cells and their progeny throughout life [15]. The mesenchymal cell population originates from a rare population of multipotent progenitor cells, currently referred to as mesenchymal stem/stromal cells (MSCs) [15][16][17].…”

“…The mesenchymal cell population originates from a rare population of multipotent progenitor cells, currently referred to as mesenchymal stem/stromal cells (MSCs) [15][16][17]. Given that MSCs have been shown to modulate not only normal B-cell proliferation and differentiation [18,19] but also the tumor growth [20], one could speculate that potential abnormalities in patient MSCs might contribute to the pathophysiology of CLL by providing malignant cells with aberrant growth/survival signals.…”