Thrombopoietin Augments Stem Cell Factor–Dependent Growth of Human Mast Cells From Bone Marrow Multipotential Hematopoietic Progenitors (original) (raw)
Related papers
The International Journal of Cell Cloning, 1987
Mast cells * Connective tissue-type mast cells Mucosal mast Interleukin 4 * Mutant mouse-Hematopoietic stem cell cells * Interleukin 3 Abstract. Information about the differentiation of mast cells has increased remarkably in the past ten years. This progress has resulted from the introduction of techniques which developed in other fields of experimental hematology. Once mast cells were recognized as a progeny of multipotential hematopoietic stem cells, their unique differentiation processes were clarified. Although most of the progeny of stem cells leave the hematopoietic tissue after maturation, undifferentiated precursors of mast cells leave the hematopoietic tissue. Morphologically, unidentifiable precursors migrate in the bloodstream, invade the connective tissues or the mucosa of the alimentary canal, proliferate, and differentiate into mast cells. Even after their morphological differentiation, some mast cells retain an extensive proliferative potential. There are at least two subpopulations of mast cells: a connective-tissue type and a mucosal type. Connective tissue-type and mucosal mast cells can be distinguished by histochemical, electron microscopical, biochemical and immunological criteria; however, these two types can interchange, and their phenotypes are determined by the anatomical microenvironment in which their final differentiation occurs. Although biochemical natures of the anatomical microenvironment are unknown, molecules that support proliferation and differentiation of mast cells in vitro have been characterized, i.e., interleukin 3 and interleukin 4. In the next ten years, increased information about the differentiation processes will probably induce further understanding of mast cell functions.
British Journal of Haematology, 1999
Stem cell factor (SCF) plays a key role in the development of mast cells from haemopoietic progenitor cells. In this study we have investigated the effect of the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By using delayed addition of SCF, we examined the potential of mast cell progenitors to keep their capacity to differentiate into mast cells after exposure to factors signalling differentiation into other lineages. Culture with either cytokine for 3 weeks before transfer to SCF-containing medium resulted in the development of mast cells in all cultures. The appearance of mast cells was attenuated when the cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells had not lost the capacity to develop into mast cells. In contrast, in cultures initiated with FL and transferred to medium containing SCF, the same amount of mast cells developed as in the SCF cultures. Thus, cells committed to the mast cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF and keep their potential to differentiate into mature mast cells.
Journal of Immunological Methods, 2008
During the last two decades different scientific groups have investigated the phenotype and function of in vitro generated human mast cells (MC). The cells have been shown to display variable surface markers and functional characteristics. The phenotypic differences may reflect different culture conditions, protocols or the use of different progenitors. To investigate the significance of different progenitors, we have compared MC generated from CD133 + progenitor cells from cord blood (CBMC) or peripheral blood (PBMC). The progenitors were cultured for 7 weeks in the presence of IL-6 and SCF, with addition of IL-3 the first 3 weeks, and FCS during week 7. The phenotype of the established MC was characterized by surface marker expression levels, metachromasia, histamine and tryptase contents and their function was evaluated by receptor-mediated release of histamine and PGD 2 . The generated metachromatic (b 99%) MC were 75% tryptase + , regardless of the source of progenitor cell. Expression of c-kit/CD117, CD203c, and FcεRI was comparable. The density of ckit/CD117 receptors on CBMC was higher that of PBMC (p b 0.001). The density of CD203c and FcεRI was higher on PBMC (p b 0.001). PBMC contained more histamine (p b 0.001), expressed more FcεRI (p b 0.001) and released more histamine (p b 0.001) and PGD 2 (p b 0.001) upon ligation of FcεRI, than CBMC. Culture with IL-4 increased expression of tryptase, FcεRI, CD117 and CD203c, secretion of histamine and PGD 2 of PBMC, and histamine secretion of CBMC. Cord and peripheral blood may give rise to different types of MC. The question addressed should determine the progenitor cell and protocol to be used.
Blood, 2003
The transplantation of primitive human cells into sublethally irradiated immune-deficient mice is the well-established in vivo system for the investigation of human hematopoietic stem cell function. Although mast cells are the progeny of hematopoietic stem cells, human mast cell development in mice that underwent human hematopoietic stem cell transplantation has not been reported. Here we report on human mast cell development after xenotransplantation of human hematopoietic stem cells into nonobese diabetic severe combined immunodeficient \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \((\mathrm{NOD{/}SCID}){/}{\gamma}_{\mathrm{c}}^{null}\) \end{document} (NOG) mice with severe combined immunodeficiency and interleukin 2 (IL-2) receptor γ-chain allelic mutation. Supported by the murine environment, human mast cell clusters developed in mouse dermis, but they required more ti...
Differentiation of mast cell subpopulations from mouse embryonic stem cells
Journal of Immunological Methods, 2012
Mast cells can generally be divided into two major groups, connective tissue mast cells and mucosal mast cells. We and others have previously shown that these mast cell populations can be developed in vitro from mouse bone marrow stem cells using a combination of specific growth factors and cytokines. Mast cell differentiation from mouse embryonic stem (ES) cells is an important alternative method when developing mast cells from an embryonic lethal genetic deficiency or to reduce the use and handling of experimental animals. In this study, we have used protocols prior known to induce connective tissue like mast cells (CTLMC) (SCF and IL-4) and mucosal like mast cells (MLMC) (SCF, IL-3, IL-9 and TGF-β) from mouse bone marrow progenitor cells and employed these protocols to study if phenotype specific mast cells can be developed from ES cells. We here demonstrate that mast cells of the different phenotypes, CTLMC and MLMC, can be derived from mouse ES cells. The mast cell populations were characterized by chymase expression, receptor expression and their difference in activation pattern and in activationinduced survival.
Development of human mast cells in vitro
Proceedings of the National Academy of Sciences, 1989
Nucleated cells of human umbilical cord blood were cocultured with mouse skin-derived 3T3 fibroblasts. After 7-8 weeks in culture, when the number of the other hematopoietic cells declined, metachromatic granule-containing mononuclear cells appeared in the cultures, and the number of the cells increased up to 12 weeks. After 11-14 weeks in culture, the metachromatic mononuclear cells comprised a substantial portion of the cultured cells. These cells contained 1.8-2 micrograms of histamine per 10(6) cells and bore receptors for IgE. All of the cells contained tryptase in their granules. Electron microscopic analysis showed that these cells were mature human mast cells, clearly different from the basophilic granulocytes or eosinophils that arise in a variety of circumstances in cord blood cell cultures. Most of the cultured mast cells expressed some granules with regular crystalline arrays and contained both tryptase and chymase, and thus resembled human skin mast cells.
The in vitro differentiation of mast cells
The Journal of Cell Biology
When cells from lymph nodes or thoracic duct of mice hyperimmunized with protein antigens are cultivated on embryo monolayers in the presence of the antigen, numerous clones of mast cells appear. The histochemical and ultrastructural characteristics of the cells permit their identification as mast cells and distinguish them from the phagocytic histiocytes that usually arise in abundance in similar cultures from unimmunized mouse cells or from immunized mouse cells cultured in the absence of the antigen. Only a few colonies of mast cells appeared in the latter cultures. The basis for the induction of mast cell differentiation is not known.
Experimental Hematology, 2005
Objectives. Thrombopoietin (TPO) is known to promote platelet number, have growthpromoting potential for human megakaryocytes (HuMKs), and increase erythrocyte, monocyte, mast cell, and granulocyte numbers in the presence of additional growth factors. We explored the ability of TPO alone or in the presence of stem cell factor (SCF) to support human mast cells (HuMCs). Methods. CD34 ϩ pluripotent and CD34 ϩ /CD117 ϩ /CD13 ϩ HuMC progenitor cells were cultured in rhTPO and examined for HuMCs. Similarly, we added rhTPO to CD34 ϩ cells cultured in stem cell factor (SCF), which promotes HuMC development. Results. When CD34 ϩ cells were cultured in 10 ng/mL rhTPO and 10 ng/mL rhSCF, TPO enhanced HuMC numbers compared to rhSCF alone. Higher concentrations of rhTPO (50 ng/mL) in the presence of 100 ng/mL rhSCF inhibited the rhSCF-dependent subpopulation of CD117 high HuMCs, while promoting CD117 low HuMCs. Human CD34 ϩ /CD117 ϩ /CD13 ϩ cells cultured in rhTPO alone for 1 to 2 weeks differentiated into CD41 ϩ /CD110 ϩ HuMKs (85-90%) and FceRI ϩ /CD117 low /CD13 ϩ HuMCs (5-10%). RhTPO-induced HuMCs expressed the TPO (CD110) receptor, tryptase, and chymase and survived when recultured in rhSCF. Conclusion. The effect of TPO on HuMCs in the presence of rhSCF varies, depending on the relative concentration of each growth factor, while TPO alone or in combination with rhSCF supports a unique population of CD117 low /CD110 ϩ HuMCs. Ć
Role of Thrombopoietin in Mast Cell Differentiation
2007
Mast cells are important elements of the body response to foreign antigens, being those represented either by small molecules (allergic response) or harbored by foreign microorganisms (response to parasite infection). These cells derive from hematopoietic stem/progenitor cells present in the marrow. However, in contrast with most of the other hematopoietic lineages, mast cells do not differentiate in the marrow but in highly vascularized extramedullary sites, such as the skin or the gut. Mast cell differentiation in the marrow is activated as part of the body response to parasites. We will review here the mast cell differentiation pathway and what is known of its major intrinsic and extrinsic control mechanisms. It will also be described that thrombopoietin, the ligand for the Mpl receptor, in addition to its pivotal rule in the control of thrombocytopoiesis and of hematopoietic stem/progenitor cell proliferation, exerts a regulatory function in mast cell differentiation. Some of the possible implications of this newly described biological activity of thrombopoietin will be discussed.