Expression of blood group genes by mesenchymal stem cells

Schäfer, Richard; Schnaidt, Martina; Klaffschenkel, Roland A.; Siegel, Georg; Schüle, Michael Christian; Rädlein, Maria Anna; Hermanutz-Klein, Ursula; Ayturan, Miriam; Buadze, Marine; Gassner, Christoph; Danielyan, Lusine; Kluba, Torsten; Northoff, Hinnak; Flegel, Willy A.

doi:10.1111/j.1365-2141.2011.08652.x

Cited by 28 publications

(22 citation statements)

References 51 publications

(61 reference statements)

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“…Studies have revealed that BM-MSC preparations in vitro are composed of poorly defined subpopulations, and that a minority of clonally expanded MSCs showed full “tri-lineage” (adipogenic, osteogenic and chondrogenic) differentiation potential [12,14,26,27], pointing toward functional differences of BM-MSC subpopulations. In addition to intra-individual heterogeneity, donor-related variations of differentiation potential and growth kinetics of MSC preparations point toward significant inter-individual heterogeneity [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Human BM-MSCs were isolated and cultured as described previously [14]. After written informed consent and approval of the ethical committee of the University Hospital Tübingen, Germany, BM from patients without metabolic or neoplastic diseases was obtained during orthopedic operations.…”

Section: Methodsmentioning

confidence: 99%

“…Functional characterization of BM-MSCs included induction of adipogenic, osteogenic and chondrogenic differentiation in vitro as described previously [14]. Briefly, for adipogenic and osteogenic differentiation, BM-MSCs were seeded at a density of 1,000 cells per cm 2 at P1 and kept under standard culture conditions until reaching subconfluency.…”

Section: Methodsmentioning

confidence: 99%

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Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells

Siegel¹,

Kluba

Hermanutz-Klein³

et al. 2013

BMC Med

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BackgroundMesenchymal stromal cells (MSCs) are attractive for cell-based therapies ranging from regenerative medicine and tissue engineering to immunomodulation. However, clinical efficacy is variable and it is unclear how the phenotypes defining bone marrow (BM)-derived MSCs as well as donor characteristics affect their functional properties.MethodsBM-MSCs were isolated from 53 (25 female, 28 male; age: 13 to 80 years) donors and analyzed by: (1) phenotype using flow cytometry and cell size measurement; (2) in vitro growth kinetics using population doubling time; (3) colony formation capacity and telomerase activity; and (4) function by in vitro differentiation capacity, suppression of T cell proliferation, cytokines and trophic factors secretion, and hormone and growth factor receptor expression. Additionally, expression of Oct4, Nanog, Prdm14 and SOX2 mRNA was compared to pluripotent stem cells.ResultsBM-MSCs from younger donors showed increased expression of MCAM, VCAM-1, ALCAM, PDGFRβ, PDL-1, Thy1 and CD71, and led to lower IL-6 production when co-cultured with activated T cells. Female BM-MSCs showed increased expression of IFN-γR1 and IL-6β, and were more potent in T cell proliferation suppression. High-clonogenic BM-MSCs were smaller, divided more rapidly and were more frequent in BM-MSC preparations from younger female donors. CD10, β1integrin, HCAM, CD71, VCAM-1, IFN-γR1, MCAM, ALCAM, LNGFR and HLA ABC were correlated to BM-MSC preparations with high clonogenic potential and expression of IFN-γR1, MCAM and HLA ABC was associated with rapid growth of BM-MSCs. The mesodermal differentiation capacity of BM-MSCs was unaffected by donor age or gender but was affected by phenotype (CD10, IFN-γR1, GD2). BM-MSCs from female and male donors expressed androgen receptor and FGFR3, and secreted VEGF-A, HGF, LIF, Angiopoietin-1, basic fibroblast growth factor (bFGF) and NGFB. HGF secretion correlated negatively to the expression of CD71, CD140b and Galectin 1. The expression of Oct4, Nanog and Prdm14 mRNA in BM-MSCs was much lower compared to pluripotent stem cells and was not related to donor age or gender. Prdm14 mRNA expression correlated positively to the clonogenic potential of BM-MSCs.ConclusionsBy identifying donor-related effects and assigning phenotypes of BM-MSC preparations to functional properties, we provide useful tools for assay development and production for clinical applications of BM-MSC preparations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells

Siegel¹,

Kluba

Hermanutz-Klein³

et al. 2013

BMC Med

Self Cite

400

349

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show abstract

“…Abbreviations: CSC cancer stem cell, ESC embryonic stem cell, HProgC hematogenic progenitor cell, iPSC induced pluripotent stem cell, MSC mesenchymal stem cell, NSC neuronal stem cell, onfFN oncofetal fibronectin, ProgC progenitor cell, PSC pluripotent stem cell.,Tang et al 2011; 2, Solter and Knowles Solter and Knowles 1978; 3, Son et al Son et al 2009; 4, Huang et al Huang et al 2009; 5, Hennen and Faissner Hennen and Faissner 2012; 6, Riethdorf et al Riethdorf et al 2006; 7, Yanagisawa et al Yanagisawa et al 2011; 8, Wenk et al Wenk et al 1994; 9, Cao et al Cao et al 2001; 10, Lin et al Lin et al 2010b; Schäfer et al 11, Schäfer et al Schäfer et al 2011; 12, Matsuura et al Matsuura et al 1988; 13, Wearne et al Wearne et al 2008Lin et al 2010a; 15, Battula et al Battula et al 2012; 16, Kannagi et al Kannagi et al 1983; 17, Henderson et al Henderson et al 2002; 18, Chang et al Chang et al 2008; 19, Carpenter et al Carpenter et al 2003; 20, Gang et al Gang et al 2007; 21, LaBarge et al LaBarge et al 2007; 22, Badcock et al Badcock et al 1999.…”

Section: Introductionmentioning

confidence: 99%

What makes cancer stem cell markers different?

2013

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Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve this problem in at least a subgroup of stem cell markers. Glycosylation may provide the key.

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“…7 While some DARC mRNA is expressed by mesenchymal stem cells, Fy antigens cannot be detected. 8 Antithetical antigens, Fy a and Fy b , are encoded by codominant allele groups FY*A and FY*B, which differ by a single-nucleotide polymorphism (SNP) 125G>A with an amino acid substitution Gly42Asp. 5,6 A homozygous single-nucleotide substitution in the 5′ UTR, -67t>c, also called GATA box mutation, leads to a lack of DARC protein in RBCs, serologically detected as Fy(a-b-), which prevents invasion by P. vivax and P. knowlesi.…”

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confidence: 99%

DARCalleles and Duffy phenotypes in African Americans

et al. 2011

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Background The DARC (Duffy blood group, chemokine receptor) gene encodes for a transmembrane glycoprotein that functions as a chemokine transporter, is a receptor for Plasmodium vivax and knowlesi, and expresses the Duffy blood group antigens (Fy). The Fy(a−b−) phenotype found in people of African descent is typically associated with a −67t>c mutation in the 5′ untranslated region (UTR), which prevents red blood cells being invaded by Plasmodium vivax and knowlesi. The aim of this study was to establish DARC allele frequencies in an African American blood donor cohort, determine a phylogenetic tree for DARC, and compare human and Neandertal DARC genes. Methods The DARC nucleotide sequence of 54 African American blood donors was determined from genomic DNA. Heterozygous substitutions were resolved by sequencing of haplotype specific amplifications. A phylogenetic tree for DARC was established using the neighbor-joining method with Pan troglodytes as root. Results 108 haplotypes of the DARC gene could be unambiguously determined from nucleotide position −300 in the 5′ UTR to +300 in the 3′ UTR. 11 different alleles were found, including the clinically relevant FY*A, FY*B, FY*B-67C, FY*B298A, and FY*X alleles. All phenotype predictions based on genotypes matched exactly the serologically determined phenotypes: 52% Fy(a−b−), 28% Fy(a−b+), and 20% Fy(a+b−). Conclusions The nucleotide sequencing approach using one amplicon is a practical genotyping method for DARC and allows the determination of haplotypes even in heterozygous constellations. We developed a phylogenetic tree for DARC alleles and postulated a distinct FY*B allele as ancestral for the extant DARC alleles in humans.

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Expression of blood group genes by mesenchymal stem cells

Cited by 28 publications

References 51 publications

Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells

Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells

What makes cancer stem cell markers different?

DARCalleles and Duffy phenotypes in African Americans

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