Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body (original) (raw)
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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.
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.
Proceedings of the National Academy of Sciences of the United States of America, 2000
An important goal of tissue engineering is to achieve reconstitution of specific functionally active cell types by transplantation of differentiated cell populations derived from normal or genetically altered embryonic stem cells in vitro. We find that mast cells derived in vitro from wild-type or genetically manipulated embryonic stem cells can survive and orchestrate immunologically specific IgE-dependent reactions after transplantation into mast cell-deficient Kit W ͞Kit W-v mice. These findings define a unique approach for analyzing the effects of mutations of any genes that are expressed in mast cells, including embryonic lethal mutations, in vitro or in vivo.
Proceedings of the …, 2000
An important goal of tissue engineering is to achieve reconstitution of specific functionally active cell types by transplantation of differentiated cell populations derived from normal or genetically altered embryonic stem cells in vitro. We find that mast cells derived in vitro from wild-type or genetically manipulated embryonic stem cells can survive and orchestrate immunologically specific IgE-dependent reactions after transplantation into mast cell-deficient Kit W ͞Kit W-v mice. These findings define a unique approach for analyzing the effects of mutations of any genes that are expressed in mast cells, including embryonic lethal mutations, in vitro or in vivo.
Blood, 1999
The effects of thrombopoietin (TPO) and/or stem cell factor (SCF) on the development of human mast cells from CD34 ؉ bone marrow (BM) cells were investigated using a serumdeprived liquid culture system. Mast cells were identified by measurement of intracellular histamine content, immunocytochemical staining, and flow cytometric analysis. Whereas SCF alone generated only a small number of tryptase ؉ cells, the addition of TPO to the culture containing SCF resulted in an apparent production of mast cells from 3 weeks until at least 15 weeks. Some of the cells reacted with an antichymase monoclonal antibody as well. Based on the effects of growth factor(s) on a later phase of the mast cell growth, TPO may stimulate an early stage of mast cell development in combination with SCF, whereas subsequent growth seems to be supported by SCF alone. Single-cell culture studies indicated that the CD34 ؉ CD38 ؊ c-kit ؉ cells and CD34 ؉ CD38 ؉ ckit ؉ cells were responsible for the SCF ؉ TPO-dependent mast cell production. Two-step culture assays clearly showed that mast cells originated from multilineage colony-forming cells that had potential to differentiate into neutrophil/mast cell lineages, neutrophil/macrophage/mast cell lineages, or neutrophil/macrophage/mast cell/erythroid lineages. These results suggest that TPO plays an important role in the development of human mast cells from CD34 ؉ BM cells in concert with SCF, and provide direct evidence of the differentiation into the mast cell lineage of human multipotential BM-derived progenitors. 1999 by The American Society of Hematology.
Journal of Immunological Methods, 2014
The identification and characterization of human mast cell (MC) functions are hindered by the shortage of MC populations suitable for investigation. Here, we present a novel technique for generating large numbers of well differentiated and functional human MCs from peripheral stem cells (= peripheral stem cell-derived MCs, PSCMCs). Innovative and key features of this technique include 1) the use of stem cell concentrates, which are routinely discarded by blood banks, as the source of CD34+ stem cells, 2) cell culture in serum-free medium and 3) the addition of LDL as well as selected cytokines. In contrast to established and published protocols that use CD34+ or CD133 + progenitor cells from full blood, we used a pre-enriched cell population obtained from stem cell concentrates, which yielded up to 10 8 differentiated human MCs per batch after only three weeks of culture starting with 10 6 total CD34+ cells. The total purity on MCs (CD117 +, FcεR1+) generated by this method varied between 55 and 90%, of which 4-20% were mature MCs that contain tryptase and chymase and show expression of FcεRI and CD117 in immunohistochemistry. PSCMCs showed robust histamine release in response to stimulation with anti-FcεR1 or IgE/anti-IgE, and increased proliferation and differentiation in response to IL-1β or IFN-γ. Taken together, this new protocol of the generation of large numbers of human MCs provides for an innovative and suitable option to investigate the biology of human MCs.
Aberrant mast-cell differentiation in mice lacking the stem-cell leukemia gene
Blood, 2007
The stem cell leukemia (SCL) gene encodes a basic helix-loop-helix transcription factor expressed in erythroid, megakaryocyte, and mast-cell lineages. SCL is essential for growth of megakaryocyte and erythroid progenitors. We have used a conditional knockout of SCL (SCL−/Δ) to examine its function in mast cells, critical effectors of the immune system. SCL−/Δ mice had markedly increased numbers of mast-cell progenitors (MCPs) within the peritoneal fluid, bone marrow, and spleen. Fractionation of bone marrow myeloid progenitors demonstrated that these MCPs were present in the megakaryocyte-erythroid–restricted cell fraction. In contrast, unilineage MCPs from control mice were present in the cell fraction with granulocyte-macrophage potential. The aberrant mast-cell differentiation of SCL−/Δ megakaryocyte-erythroid progenitors was associated with increased expression of GATA-2. Despite increased numbers of MCPs in SCL−/Δ mice, numbers of mature tissue mast cells were not increased unl...
Journal of Immunological Methods, 2000
The in vitro development of human mast cells from fetal liver cells with recombinant human stem cell factor in serum-containing RPMI was compared to that in AIM-V media with and without serum. Compared to serum-containing media, AIM-V medium caused mast cells to develop earlier and in greater numbers. By 2 weeks, about 60% of cells in serum-free AIM-V medium were phenotypic mast cells, |2 times the percentages in serum-containing media. By 6 weeks the percentages of mast cells were $80% under all conditions, but the number of mast cells was 3-4-fold greater in serum-free AIM-V medium than in serum-supplemented media. Mast cells obtained in serum-free AIM-V medium exhibited rounded nuclei, like tissue-derived mast cells; mast cells obtained in serum-supplemented media had segmented nuclei. By 10-12 weeks of culture about 40% of the AIM-V-derived cells showed strong chymase immunocytochemical staining, a pattern observed for only 14% of the cells in serum-containing media. AIM-V medium is a suitable medium for the development of human mast cells in vitro, and permits an earlier, more selective and greater expansion of mast cells than serum-containing media.