Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Honczarenko, Marek; Le, Yi; Swierkowski, Marcin; Ghiran, Ionita; Glodek, Aleksandra M.; Silberstein, Leslie E.

doi:10.1634/stemcells.2005-0319

Cited by 616 publications

(516 citation statements)

References 63 publications

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“…However, since MSCs express a range of chemokine receptors, 16 their mobilization probably occur in response to proinflammatory cytokines (such as TNF-␣, interleukin-1) released in response to fracture. 3 TNF-␣ is known to promote mobilization 17 and osteogenic differentiation of MSCs, 18 and absence of TNF-␣ impairs bone healing.…”

Section: Discussionmentioning

confidence: 99%

Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

Alm

Koivu

Heino

et al. 2010

Journal Orthopaedic Research

108

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ABSTRACT:We examined the presence of circulating plastic adherent multipotent mesenchymal stem cells (MSCs) in fracture patients. Three patient groups (n = 10-18) were evaluated, including elderly females with a femoral neck fracture treated with cemented hemiarthroplasty, an age-and sex-matched group with hip osteoarthritis (OA) treated with cemented total hip arthroplasty (THA), and younger adults with surgically treated lower extremity fractures. The presence of circulating MSCs pre-and postoperatively was compared to bone marrow (BM) MSCs from the same subjects. Criteria for identifying MSCs included cell surface markers (CD105+, CD73+, CD90+, CD45−, CD14−), proliferation through several passages as well as osteogenic, chondrogenic, and adipogenic differentiation. Plastic adherent MSCs were found in peripheral blood (PB) from 22% of hip fracture patients, 46% of younger fracture patients, and in none of 63 pre-and postmenopausal women with hip OA. When detectable, circulating MSCs appeared between 39 and 101 h after fracture. PB derived MSCs did not differ from BM derived MSCs, except for a small population (<15%) of CD34+ cells among PB derived MSCs. This initial study indicates mobilization of MSCs into the circulation in response to fracture, even in very old patients, while circulating MSCs were not detectable before or after elective THA.

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Section: Discussionmentioning

confidence: 99%

Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

Alm

Koivu

Heino

et al. 2010

Journal Orthopaedic Research

108

View full text Add to dashboard Cite

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“…MSC can also produce a variety of growth factors, cytokines, chemokines and proteases that are likely to play a role either in their immunomodulatory or in their migratory function [29][30][31]. In this respect, MSC have been shown to express a restricted pattern of chemokine receptors, including CXCR4, allowing them to migrate to tissues upon specific chemotactic triggers [32][33][34][35]. These features are likely to represent the basis for MSC homing to multiple organs where they undergo a program of tissue-specific differentiation [36].…”

Section: Immunological Phenotype and Functions Of Mscmentioning

confidence: 99%

Immunoregulatory function of mesenchymal stem cells

2006

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Mesenchymal stem cells (MSC) are a rare subset of stem cells residing in the bone marrow where they closely interact with hematopoietic stem cells and support their growth and differentiation. MSC can differentiate into multiple mesenchymal and non‐mesenchymal lineages, providing a promising tool for tissue repair. In addition, MSC suppress many T cell, B cell and NK cell functions and may affect also dendritic cell activities. Due to their limited immunogenicity, MSC are poorly recognized by HLA‐incompatible hosts. Based on these unique properties, MSC are currently under investigation for their possible use to treat immuno‐mediated diseases. However, both their condition of immunoprivilege and their immunosuppressive function have recently been challenged when analyzed under particular experimental conditions. Thus, it is likely that MSC effects on the immune system may be deeply influenced not only by cell‐to‐cell interactions, but also by environmental factors shaping their phenotype and functions.

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“…CXCL6 and CCL20, were up-regulated by LPS in the presence of dlk1. Recently, Honczarenko et al (71) have shown that hMSC cells express certain CC and CXC chemokine receptors as well as their ligands, which have been reported to play a role in controlling the proliferation and differentiation of hMSC (71). The production of chemokines by osteoblastic cells has been demonstrated to play a role in the bone inflammatory response because of infection.…”

Section: Genementioning

confidence: 99%

dlk1/FA1 Regulates the Function of Human Bone Marrow Mesenchymal Stem Cells by Modulating Gene Expression of Pro-inflammatory Cytokines and Immune Response-related Factors

Abdallah

Boissy

Tan

et al. 2007

Journal of Biological Chemistry

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dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-B. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response.

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Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors

Abstract: ABSTRACT

Cited by 616 publications

References 63 publications

Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients

Immunoregulatory function of mesenchymal stem cells

dlk1/FA1 Regulates the Function of Human Bone Marrow Mesenchymal Stem Cells by Modulating Gene Expression of Pro-inflammatory Cytokines and Immune Response-related Factors

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