Dextran Sulfate and Stromal Cell Derived Factor-1 Promote CXCR4 Expression and Improve Bone Marrow Homing Efficiency of Infused Hematopoietic Stem Cells

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.

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Bone marrow stromal cells induce myeloid and lymphoid development of the sorted hematopoietic stem cells in vitro

Blood ◽

10.1182/blood.v86.7.2590.2590 ◽

1995 ◽

Vol 86 (7) ◽

pp. 2590-2597 ◽

Cited By ~ 17

Author(s):

R Okuyama ◽

M Koguma ◽

N Yanai ◽

M Obinata

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Stromal Cell ◽

Simian Virus 40 ◽

Simian Virus ◽

T Antigen ◽

Stem Cell Population ◽

Hematopoietic Stem

Abstract Regulation of development of hematopoietic stem cells was examined by culturing Lin- c-Kit+ Sca1+ stem cells sorted from bone marrow (BM) cells by fluorescence-activated cell sorting on a layer of TBR59, a BM stromal cell line established from simian virus 40 T-antigen gene transgenic mice. The sorted stem cells did not show self-renewal, but two waves (at 7 and 13 days) of a cobblestone formation were induced by the stromal cell layer. The cobblestones were formed by finite cell division (eight divisions on average) of sorted Lin-c-Kit+ Sca1+ stem cells, and divided cells were still immature. The c-Kithigh stem cell population was induced to form the first wave of cobblestone formation committed to myeloid lineage, whereas c-Kitlow population was induced to form the second wave of this formation committed to lymphoid lineage. Both cobblestone formations require c-Kit function, but very late activation antigen-4-vascular cell adhesion molecule-1 interaction plays different parts in the two lineages.

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Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

Blood ◽

10.1182/blood.v83.2.361.361 ◽

1994 ◽

Vol 83 (2) ◽

pp. 361-369 ◽

Cited By ~ 57

Author(s):

PE Funk ◽

PW Kincade ◽

PL Witte

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Stromal Cells ◽

Stromal Cell ◽

Hematopoietic Cells ◽

Hematopoietic Stem ◽

Factor C

Abstract In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.

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283. Mobilization of Hematopoietic Stem Cells and Progenitor Cells to Lung by Intratracheal Administration of an Adenovirus Encoding Stromal Cell-Derived Factor-1

Molecular Therapy ◽

10.1016/s1525-0016(16)40725-2 ◽

2003 ◽

Vol 7 (5) ◽

pp. S112 ◽

Cited By ~ 1

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Progenitor Cells ◽

Stromal Cell ◽

Intratracheal Administration ◽

Hematopoietic Stem ◽

Stromal Cell Derived Factor

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Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during the bone repair process

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00253.2015 ◽

2016 ◽

Vol 310 (1) ◽

pp. E15-E23 ◽

Cited By ~ 14

Author(s):

Kiyotaka Okada ◽

Naoyuki Kawao ◽

Masato Yano ◽

Yukinori Tamura ◽

Shinzi Kurashimo ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stromal Cell ◽

Bone Repair ◽

Local Treatment ◽

Repair Process ◽

Femoral Bone ◽

Hematopoietic Stem ◽

Bone Damage ◽

Stromal Cell Derived Factor

Osteoblasts, osteoclasts, chondrocytes, and macrophages that participate in the bone repair process are derived from hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). However, the roles of these stem cells during the repair of injured bone tissue are still unclear. In the present study, we examined the effects of bone defect on HSCs and MSCs in bone marrow and spleen in 75 mice and its mechanism. We analyzed the HSC and MSC populations in these tissues of a mouse with femoral bone damage by using flow cytometry. The number of HSCs in the bone marrow of mice with damaged femurs was significantly lower than the number of these cells in the bone marrow of the contralateral intact femurs on day 2 after injury. Meanwhile, the number of MSCs in the bone marrow of mice with damaged femurs was significantly higher than that of the contralateral femurs. Both intraperitoneal administration of AMD3100, a C-X-C chemokine receptor 4 (CXCR4) antagonist, and local treatment with an anti-stromal cell-derived factor-1 (SDF-1) antibody blunted the observed decrease in HSC and increase in MSC populations within the bone marrow of injured femurs. In conclusion, the present study revealed that there is a concurrent decrease and increase in the numbers of HSCs and MSCs, respectively, in the bone marrow during repair of mouse femoral bone damage. Furthermore, the SDF-1/CXCR4 system was implicated as contributing to the changes in these stem cell populations upon bone injury.

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Bone marrow stromal cells induce myeloid and lymphoid development of the sorted hematopoietic stem cells in vitro

Blood ◽

10.1182/blood.v86.7.2590.bloodjournal8672590 ◽

1995 ◽

Vol 86 (7) ◽

pp. 2590-2597

Author(s):

R Okuyama ◽

M Koguma ◽

N Yanai ◽

M Obinata

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Stromal Cell ◽

Simian Virus 40 ◽

Simian Virus ◽

T Antigen ◽

Stem Cell Population ◽

Hematopoietic Stem

Regulation of development of hematopoietic stem cells was examined by culturing Lin- c-Kit+ Sca1+ stem cells sorted from bone marrow (BM) cells by fluorescence-activated cell sorting on a layer of TBR59, a BM stromal cell line established from simian virus 40 T-antigen gene transgenic mice. The sorted stem cells did not show self-renewal, but two waves (at 7 and 13 days) of a cobblestone formation were induced by the stromal cell layer. The cobblestones were formed by finite cell division (eight divisions on average) of sorted Lin-c-Kit+ Sca1+ stem cells, and divided cells were still immature. The c-Kithigh stem cell population was induced to form the first wave of cobblestone formation committed to myeloid lineage, whereas c-Kitlow population was induced to form the second wave of this formation committed to lymphoid lineage. Both cobblestone formations require c-Kit function, but very late activation antigen-4-vascular cell adhesion molecule-1 interaction plays different parts in the two lineages.

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Involvement of CXCR4 in Normal and Abnormal Development

Cells ◽

10.3390/cells8020185 ◽

2019 ◽

Vol 8 (2) ◽

pp. 185 ◽

Cited By ~ 22

Author(s):

Nanako Kawaguchi ◽

Ting-Ting Zhang ◽

Toshio Nakanishi

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stromal Cell ◽

Molecular Signature ◽

Abnormal Development ◽

Hematopoietic Stem ◽

Cell Microenvironment ◽

Stromal Cell Derived Factor ◽

And Migration ◽

Cxcr4 Axis

CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.

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