Markus G. Manz

Bio: Markus G. Manz is an academic researcher from University of Zurich. The author has contributed to research in topics: Haematopoiesis & Stem cell. The author has an hindex of 61, co-authored 243 publications receiving 20361 citations. Previous affiliations of Markus G. Manz include University of Tübingen & Stanford University.

Development of Monocytes, Macrophages, and Dendritic Cells

Abstract: Monocytes and macrophages are critical effectors and regulators of inflammation and the innate immune response, the immediate arm of the immune system. Dendritic cells initiate and regulate the highly pathogen-specific adaptive immune responses and are central to the development of immunologic memory and tolerance. Recent in vivo experimental approaches in the mouse have unveiled new aspects of the developmental and lineage relationships among these cell populations. Despite this, the origin and differentiation cues for many tissue macrophages, monocytes, and dendritic cell subsets in mice, and the corresponding cell populations in humans, remain to be elucidated.

Granulocyte-Macrophage Progenitors as Candidate Leukemic Stem Cells in Blast-Crisis CML

Abstract: methods We used fluorescence-activated cell sorting to isolate hematopoietic stem cells, common myeloid progenitors, granulocyte–macrophage progenitors, and megakaryocyte–erythroid progenitors from marrow during several phases of CML and from normal marrow. BCR-ABL, b -catenin , and LEF-1 transcripts were compared by means of a quantitative reverse-transcriptase–polymerase-chain-reaction assay in normal and CML hematopoietic stem cells and granulocyte–macrophage progenitors. Confocal fluorescence microscopy and a lymphoid enhancer factor/T-cell factor reporter assay were used to detect nuclear b -catenin in these cells. In vitro replating assays were used to identify self-renewing cells as candidate leukemic stem cells, and the dependence of self-renewal on b -catenin activation was tested by lentiviral transduction of hematopoietic progenitors with axin, an inhibitor of the b -catenin pathway. results The granulocyte–macrophage progenitor pool from patients with CML in blast crisis and imatinib-resistant CML was expanded, expressed BCR-ABL, and had elevated levels of nuclear b -catenin as compared with the levels in progenitors from normal marrow. Unlike normal granulocyte–macrophage progenitors, CML granulocyte–macrophage progenitors formed self-renewing, replatable myeloid colonies, and in vitro self-renewal capacity was reduced by enforced expression of axin. conclusions Activation of b -catenin in CML granulocyte–macrophage progenitors appears to enhance the self-renewal activity and leukemic potential of these cells.

Biology of hematopoietic stem cells and progenitors: implications for clinical application.

Abstract: Stem cell biology is scientifically, clinically, and politically a current topic. The hematopoietic stem cell, the common ancestor of all types of blood cells, is one of the best-characterized stem cells in the body and the only stem cell that is clinically applied in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Multicolor cell sorting enables the purification not only of hematopoietic stem cells, but also of their downstream progenitors such as common lymphoid progenitors and common myeloid progenitors. Recent genetic approaches including gene chip technology have been used to elucidate the gene expression profile of hematopoietic stem cells and other progenitors. Although the mechanisms that control self-renewal and lineage commitment of hematopoietic stem cells are still ambiguous, recent rapid advances in understanding the biological nature of hematopoietic stem and progenitor cells have broadened the potential application of these cells in the treatment of diseases.

Development of a human adaptive immune system in cord blood cell-transplanted mice.

Abstract: Because ethical restrictions limit in vivo studies of the human hemato-lymphoid system, substitute human to small animal xenotransplantation models have been employed. Existing models, however, sustain only limited development and maintenance of human lymphoid cells and rarely produce immune responses. Here we show that intrahepatic injection of CD34+ human cord blood cells into conditioned newborn Rag2-/-gammac-/- mice leads to de novo development of B, T, and dendritic cells; formation of structured primary and secondary lymphoid organs; and production of functional immune responses. This provides a valuable model to study development and function of the human adaptive immune system in vivo.

Langerhans cells renew in the skin throughout life under steady-state conditions

Abstract: Langerhans cells (LCs) are bone marrow (BM)–derived epidermal dendritic cells (DCs) that represent a critical immunologic barrier to the external environment, but little is known about their life cycle Here, we show that in lethally irradiated mice that had received BM transplants, LCs of host origin remained for at least 18 months, whereas DCs in other organs were almost completely replaced by donor cells within 2 months In parabiotic mice with separate organs, but a shared blood circulation, there was no mixing of LCs However, in skin exposed to ultraviolet light, LCs rapidly disappeared and were replaced by circulating LC precursors within 2 weeks The recruitment of new LCs was dependent on their expression of the CCR2 chemokine receptor and on the secretion of CCR2-binding chemokines by inflamed skin These data indicate that under steady-state conditions, LCs are maintained locally, but inflammatory changes in the skin result in their replacement by blood-borne LC progenitors

Monocyte and macrophage heterogeneity

Abstract: Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. However, as we discuss here, recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues. These advances in our understanding have implications for the development of therapeutic strategies that are targeted to modify particular subpopulations of monocytes.

Protective and pathogenic functions of macrophage subsets

Abstract: Macrophages are strategically located throughout the body tissues, where they ingest and process foreign materials, dead cells and debris and recruit additional macrophages in response to inflammatory signals They are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals In this Review, we discuss the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis We also discuss the protective and pathogenic functions of the various macrophage subsets in antimicrobial defence, antitumour immune responses, metabolism and obesity, allergy and asthma, tumorigenesis, autoimmunity, atherosclerosis, fibrosis and wound healing Finally, we briefly discuss the characterization of macrophage heterogeneity in humans