Phenotypic and Functional Evidence for the Expression of CD4 by Hematopoietic Stem Cells Isolated From Human Fetal Liver

Muench, Marcus O.; Roncarolo, Maria Grazia; Namikawa, Reiko

doi:10.1182/blood.v89.4.1364

Cited by 60 publications

(25 citation statements)

References 56 publications

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“…There was apparently no “cluster” of lymphocytes in the liver that acts as a focus of lymphocyte proliferation and differentiation. In contrast, previous cytometric studies found that commercially obtained human fetal liver at 12–32 weeks of gestation contained many CD4‐ or CD8‐positive T lymphocytes (Bárcene et al, ; Muench et al, ), whereas another study found few CD4‐ or CD8‐positive cells, but many CD7+CD45+ cells, in the fetal liver (Carding et al, ). Similarly, cytometric studies showed involvement of the fetal liver and spleen in B lymphocyte differentiation (Bofill et al, ; Erbach et al, ; Settmacher et al, ).…”

Section: Discussionmentioning

confidence: 83%

Lymphocyte Subpopulations in the Liver, Spleen, Intestines, and Mesenteric Nodes: An Immunohistochemical Study Using Human Fetuses at 15–16 Weeks

Hwang

Kim

et al. 2014

The Anatomical Record

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The roles of the liver and intestines in lymphocyte differentiation in human fetuses were assessed by immunohistochemical analysis of the thymus, bone marrow, liver, spleen, intestines, and lymph nodes of 15-16 week human fetuses using primary antibodies against IgM, CD3, CD7, CD8, CD10, CD20, CD45RO, HLA-DR, and CD68. The density of immunoreactive lymphocytes was high in the thymus and lymph nodes, but much lower in the bones, liver, spleen, and intestines. The medulla of the thymus contained IgM-positive mature B lymphocytes as well as CD20-positve B lymphocytes. In contrast, CD10-positive immature B lymphocytes were restricted in the cortex. There were no site-dependent differences among axillary, mediastinal, mesenteric, and pelvic lymph nodes. CD68-positive cells were observed at all sites examined. Many HLA-DR-positive round cells were present in the thymus, with fewer in the liver and spleen. The absolute number of lymphocytes was estimated to be 10-fold higher in lymph nodes than in liver. Although limited by analysis of only one fetal stage, these findings suggest that mesenteric nodes are likely to be more important than the liver, spleen, and intestines for lymphocyte proliferation and differentiation in human mid-term fetuses.

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Section: Discussionmentioning

confidence: 83%

Lymphocyte Subpopulations in the Liver, Spleen, Intestines, and Mesenteric Nodes: An Immunohistochemical Study Using Human Fetuses at 15–16 Weeks

Hwang

Kim

et al. 2014

The Anatomical Record

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“…For fetuses ≥ 20 weeks' gestation, the content of CD34 +/++ cells was a median 1·17 × 10 8 cells (Table I). Fetal HSCs are believed to represent a small subpopulation of cells expressing high levels of CD34 (Di Giusto et al , 1994) and there is evidence to suggest that they are enriched among CD38 − , CD4 + and/or CD90 + cells (Baum et al , 1992; Craig et al , 1993; Muench et al , 1994a, 1997; Bárcena et al , 1995; Waller et al , 1995; Humeau et al , 1997; Roy et al , 1997). We used flow cytometry to estimate the HSC content of FBM based on these phenotypically defined, and overlapping (Muench et al , 1997), cell populations (Table I).…”

Section: Resultsmentioning

confidence: 99%

“…Only a minority of CD34 +/++ cells are HSCs responsible for durable engraftment. In fetal tissues, these HSCs have been tentatively defined as CD34 ++ CD4 + , CD34 ++ CD90 + or CD34 ++ CD38 − (Baum et al , 1992; Craig et al , 1993; Muench et al , 1994a, 1997; Bárcena et al , 1995; Waller et al , 1995; Humeau et al , 1997; Roy et al , 1997). In FBM samples between 20 and 24 weeks' gestation, the median content of CD34 ++ CD4 + cells was 1·37 × 10 6 and the median number of CD34 ++ CD90 + cells was 2·20 × 10 6.…”

Section: Discussionmentioning

confidence: 99%

Fetal bone marrow as a source of stem cells for in utero or postnatal transplantation

Golfier¹,

Bárcena

Harrison

et al. 2000

Br J Haematol

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We examined the potential of human fetal bone marrow (FBM) as a source of haematopoietic stem cells for transplantation. The median number of cells obtained between 20 and 24 weeks' gestation was 1·9 × 109 and a median 1·17 × 108 of these cells expressed CD34. Flow cytometry was also used to estimate the content of three different candidate stem cell populations in the tissues older than 20 weeks' gestation. A median 8·8 × 105 CD34++CD38− cells, 1·37 × 106 CD34++CD4+ cells and 2·20 × 106 CD34++CD90+ cells were detected. The content of colony‐forming units culture (CFU‐C) in the FBM ranged from 2·8 × 104 to 6·0 × 106 per fetus. The CFU‐C content could be expanded 50‐fold by culture for 1 week in serum‐deprived medium and the growth factors kit ligand and granulocyte–macrophage colony‐stimulating factor. Positive selection of FBM CD34+/++ cells was achieved using the Baxter Isolex 50 device. An average purity of 82% and yield of up to 19% of CD34+/++ cells was achieved. T cells were depleted by 99·84%. Analysis of candidate stem cell populations and primitive CFU‐C suggested a preferential enrichment of these cells over the total population of CD34+/++ cells. All FBM samples were found to be free of microbial contamination at the time of harvest and after selection of CD34+/++ cells. Thus, FBM is a safe source of stem cells. The large number of progenitors and candidate stem cells that can be obtained from FBM makes it suitable for in utero and possibly postnatal transplantation.

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“…Low levels of human cells were detectable in the marrow or peripheral tissues of the scid mouse hosts [25]. Investigators have used SCID-hu mice as model systems for the study of human stem cell phenotype and differentiation [42][43][44][45][46][47][48][49][50][51][52], human gene therapy protocols [53][54][55], human T-cell differentiation [56], and homing of human myeloma cells to the bone marrow [57]. SCID-hu mice, in combination with cotransplanted thymic fragments, have been used to investigate the primitive hemopoietic stem cell that populates the T-cell lineage [42,58], for studies of human T-cell function [59,60], and for infection of human T cells and thymus with HIV [61,62].…”

Section: Scid-hu Micementioning

confidence: 99%

SCID Mouse Models of Human Stem Cell Engraftment

1998

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The discovery of the severe combined immunodeficiency (scid) mouse mutation has provided a tool for establishment of small animal models as hosts for the in vivo analysis of normal and malignant human pluripotent hemopoietic stem cells. Intravenous injection of irradiated scid mice with human bone marrow, cord blood, or G-CSF cytokine-mobilized peripheral blood mononuclear cells, all rich in human hemopoietic stem cell activity, results in the engraftment of a human hemopoietic system in the murine recipient. This model has been used to identify a pluripotent stem cell, termed "scid-repopulating cell" (SRC) that is more primitive than any of the hemopoietic stem cell populations identified using the currently available in vitro methodology. In this review, we describe the development and use of this model

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Phenotypic and Functional Evidence for the Expression of CD4 by Hematopoietic Stem Cells Isolated From Human Fetal Liver

Cited by 60 publications

References 56 publications

Lymphocyte Subpopulations in the Liver, Spleen, Intestines, and Mesenteric Nodes: An Immunohistochemical Study Using Human Fetuses at 15–16 Weeks

Lymphocyte Subpopulations in the Liver, Spleen, Intestines, and Mesenteric Nodes: An Immunohistochemical Study Using Human Fetuses at 15–16 Weeks

Fetal bone marrow as a source of stem cells for in utero or postnatal transplantation

SCID Mouse Models of Human Stem Cell Engraftment

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