Molecular-genetic and immunophenotypic analysis of antigen profile and osteogenic and adipogenic potentials of mesenchymal stromal cells from fetal liver and adult bone marrow in rats

We have previously shown that the HCA/ALCAM (CD166) glycoprotein, a member of the immunoglobulin family that mediates both homophilic and heterophilic cell-cell adhesion, via the CD6 ligand, is expressed at the surface of all of the most primitive CD38−/lo, Thy-1+, rho123lo, CD34+hematopoietic cells in human fetal liver and fetal and adult bone marrow. In the present report we show that HCA is also expressed by subsets of stromal cells in the primary hematopoietic sites that sequentially develop in the human embryo and fetus, ie, the paraaortic mesoderm, liver, thymus, and bone marrow. Adult bone marrow stromal cells established in vitro, including those derived from Stro-1+ progenitors and cells from immortalized cell lines, express HCA. In contrast, no HCA expression could be detected in peripheral lymphoid tissues, fetal spleen, and lymph nodes. HCA membrane molecules purified from marrow stromal cells interact with intact marrow stromal cells, CD34+ CD38−hematopoietic precursors, and CD3+ CD6+peripheral blood lymphocytes. Finally, low but significant levels of CD6 are here for the first time detected at the surface of CD34+ rho123med/lo progenitors in the bone marrow and in mobilized blood from healthy individuals. Altogether, these results indicate that the HCA/ALCAM surface molecule is involved in homophilic or heterophilic (with CD6) adhesive interactions between early hematopoietic progenitors and associated stromal cells in primary blood-forming organs.

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HCA, an Immunoglobulin-Like Adhesion Molecule Present on the Earliest Human Hematopoietic Precursor Cells, Is Also Expressed by Stromal Cells in Blood-Forming Tissues

Blood ◽

10.1182/blood.v93.3.826 ◽

1999 ◽

Vol 93 (3) ◽

pp. 826-837 ◽

Cited By ~ 62

Author(s):

Fernando Cortés ◽

Frédéric Deschaseaux ◽

Nobuko Uchida ◽

Marie-Claude Labastie ◽

Annabelle M. Friera ◽

...

Keyword(s):

Bone Marrow ◽

Stromal Cells ◽

Fetal Liver ◽

Present Report ◽

Marrow Stromal Cells ◽

Lymphoid Tissues ◽

Adult Bone Marrow ◽

Adhesive Interactions ◽

Adult Bone

Abstract We have previously shown that the HCA/ALCAM (CD166) glycoprotein, a member of the immunoglobulin family that mediates both homophilic and heterophilic cell-cell adhesion, via the CD6 ligand, is expressed at the surface of all of the most primitive CD38−/lo, Thy-1+, rho123lo, CD34+hematopoietic cells in human fetal liver and fetal and adult bone marrow. In the present report we show that HCA is also expressed by subsets of stromal cells in the primary hematopoietic sites that sequentially develop in the human embryo and fetus, ie, the paraaortic mesoderm, liver, thymus, and bone marrow. Adult bone marrow stromal cells established in vitro, including those derived from Stro-1+ progenitors and cells from immortalized cell lines, express HCA. In contrast, no HCA expression could be detected in peripheral lymphoid tissues, fetal spleen, and lymph nodes. HCA membrane molecules purified from marrow stromal cells interact with intact marrow stromal cells, CD34+ CD38−hematopoietic precursors, and CD3+ CD6+peripheral blood lymphocytes. Finally, low but significant levels of CD6 are here for the first time detected at the surface of CD34+ rho123med/lo progenitors in the bone marrow and in mobilized blood from healthy individuals. Altogether, these results indicate that the HCA/ALCAM surface molecule is involved in homophilic or heterophilic (with CD6) adhesive interactions between early hematopoietic progenitors and associated stromal cells in primary blood-forming organs.

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Leptin-Receptor-Expressing Mesenchymal Stromal Cells Represent the Main Source of Bone Formed by Adult Bone Marrow

Cell Stem Cell ◽

10.1016/j.stem.2014.06.008 ◽

2014 ◽

Vol 15 (2) ◽

pp. 154-168 ◽

Cited By ~ 558

Author(s):

Bo O. Zhou ◽

Rui Yue ◽

Malea M. Murphy ◽

James G. Peyer ◽

Sean J. Morrison

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Leptin Receptor ◽

Adult Bone Marrow ◽

Adult Bone

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Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow

Cell Stem Cell ◽

10.1016/j.stem.2016.02.015 ◽

2016 ◽

Vol 18 (6) ◽

pp. 782-796 ◽

Cited By ~ 165

Author(s):

Rui Yue ◽

Bo O. Zhou ◽

Issei S. Shimada ◽

Zhiyu Zhao ◽

Sean J. Morrison

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Leptin Receptor ◽

Adult Bone Marrow ◽

Adult Bone

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BMPRIA is required for osteogenic differentiation and RANKL expression in adult bone marrow mesenchymal stromal cells

Scientific Reports ◽

10.1038/s41598-018-26820-8 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 8

Author(s):

Soma Biswas ◽

Ping Li ◽

Hongguang Wu ◽

Md Shafiquzzaman ◽

Shunichi Murakami ◽

...

Keyword(s):

Bone Marrow ◽

Osteogenic Differentiation ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Rankl Expression ◽

Adult Bone Marrow ◽

Adult Bone

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Faculty Opinions recommendation of Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718463146.793498075 ◽

2014 ◽

Author(s):

Louise Purton ◽

Alanna Green

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Leptin Receptor ◽

Adult Bone Marrow ◽

Adult Bone

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Human fetal liver MSCs are more effective than adult bone marrow MSCs for their immunosuppressive, immunomodulatory, and Foxp3+ T reg induction capacity

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02176-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yi Yu ◽

Alejandra Vargas Valderrama ◽

Zhongchao Han ◽

Georges Uzan ◽

Sina Naserian ◽

...

Keyword(s):

Bone Marrow ◽

T Cells ◽

Immune Responses ◽

Molecular Mechanisms ◽

Fetal Liver ◽

Cytotoxic T Cells ◽

Cell Contact ◽

Adult Bone Marrow ◽

Adult Bone

Abstract Background Mesenchymal stem cells (MSCs) exhibit active abilities to suppress or modulate deleterious immune responses by various molecular mechanisms. These cells are the subject of major translational efforts as cellular therapies for immune-related diseases and transplantations. Plenty of preclinical studies and clinical trials employing MSCs have shown promising safety and efficacy outcomes and also shed light on the modifications in the frequency and function of regulatory T cells (T regs). Nevertheless, the mechanisms underlying these observations are not well known. Direct cell contact, soluble factor production, and turning antigen-presenting cells into tolerogenic phenotypes, have been proposed to be among possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion and activity. We and others demonstrated that adult bone marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ helper and CD8+ cytotoxic T cells but also indirectly through the induction of T regs. In parallel, we demonstrated that fetal liver (FL)-MSCs demonstrates much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs. Methods MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation, and their proliferation potential. Using different in vitro combinations, we performed co-cultures of FL- or BM-MSCs and murine CD3+CD25−T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results We demonstrated that although both types of MSC display similar cell surface phenotypic profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs. Conclusions These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.

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