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  • 1
    Language: English
    In: Annals of the Rheumatic Diseases, March, 2014, Vol.73(3), p.A27(2)
    Keywords: Interleukin-7 -- Physiological Aspects ; Interleukin-7 -- Research ; Rheumatoid Arthritis -- Care And Treatment ; Rheumatoid Arthritis -- Research ; B Cells -- Physiological Aspects ; B Cells -- Research
    ISSN: 0003-4967
    Source: Cengage Learning, Inc.
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  • 2
    Language: English
    In: Annals of the Rheumatic Diseases, 26 September 2010, Vol.69(9), p.1636
    Description: Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy.
    Keywords: Medicine;
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 3
    Language: English
    In: Arthritis & Rheumatism, August 2012, Vol.64(8), pp.2632-2643
    Description: Objective Controversy surrounds the identity and functionality of rare bone marrow-derived multipotential stromal cells (BM-MSCs), including their differentiation capabilities, their relationship to pericytes and hematopoiesis-supporting stromal cells, and the relevance of their culture-expanded progeny in studies of skeletal biology and development of cell-based therapies. The aim of this study was to clarify the nature of candidate BM-MSCs by profiling transcripts that reflect different aspects of their putative functions in vivo. Methods Rare, sorted BM-derived CD45 super(-/low) CD271 super(bright) (CD271) cells were analyzed using 96-gene expression arrays focused on transcripts relevant to mesenchymal-lineage differentiation (toward bone, cartilage, fat, or muscle), hematopoietic and stromal support, and molecules critical to skeletal homeostasis. These cells were compared to matched CD45+ CD271- hematopoietic-lineage cells, culture-expanded MSCs, and skin fibroblasts. When feasible, transcription was validated using flow cytometry. Results CD271 cells had a transcriptional profile consistent with the multiple fates of in vivo MSCs, evident from the observed simultaneous expression of osteogenic, adipogenic, pericytic, and hematopoiesis-supporting genes (e.g., SP7 [osterix], FABP4 [fatty acid binding protein 4], ANGPT1 [angiopoietin 1], and CXCL12 [stromal cell-derived factor 1], respectively). Compared to culture-expanded MSCs and fibroblasts, CD271 cells exhibited greater transcriptional activity, particularly with respect to Wnt-related genes (〉1,000-fold increased expression of FRZB [secreted frizzled-related protein 3] and WIF1 [Wnt inhibitory factor 1]). A number of transcripts were identified as novel markers of MSCs. Conclusion The native, BM-derived in vivo MSC population is endowed with a gene signature that is compatible with multiple functions, reflecting the topographic bone niche of these cells, and their signature is significantly different from that of culture-expanded MSCs. This indicates that studies of the biologic functions of MSCs in musculoskeletal diseases, including osteoporosis and osteoarthritis, should focus on in vivo MSCs, rather than their culture-adapted progeny.
    Keywords: Angiopoietin ; Sdf-1 Protein ; Cartilage Diseases ; Wnt Protein ; Stromal Cells ; Osteoarthritis ; Muscles ; Bone Marrow ; Transcription ; Homeostasis ; Fatty Acid-Binding Protein ; Fibroblasts ; Flow Cytometry ; Gene Expression ; Differentiation ; Frizzled-Related Protein 3 ; Progeny ; Cxcl12 Protein ; Signal Transduction ; Cartilage and Cartilage Diseases;
    ISSN: 0004-3591
    E-ISSN: 1529-0131
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  • 4
    Language: English
    In: Annals of the Rheumatic Diseases March 2014, Vol.73(Suppl 1), p.A27
    Description: RA is a very heterogeneous disease, recently highlighted by distinct differences in the genetic contribution to APCA(+) and ACAP(–) disease suggesting two divergent pathogenic models, with different rates of progression and response to treatment. Synovial tissue studies showed that the cellular composition of synovial membrane is relatively consistent however the size of the inflammatory cell infiltrate is variable in direct relation to local levels of inflammation and sometimes highly organised with germinal centre like structures (GCL). The role of IL-7 as an essential factor in tissue organisation has recently been recognised and we hypothesize that the synovial tissue architecture (TA) may be driven by IL-7 expression in RA.
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 5
    In: Rheumatology, 2017, Vol. 56(3), pp.488-493
    Description: Objectives. The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis. Methods. The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used. Results. Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation ( P = 0.008) and migration ( P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone ( P 〈 0.05). MSC osteogenesis was enhanced following IL-22 exposure ( P = 0.03, measured by calcium production). The combination of IFN-γ and TNF with or without IL-22 suppressed MSC osteogenesis ( P = 0.03). Conclusion. This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.
    Keywords: Spondyloarthropathy ; Mesenchymal Stem Cells ; Il - 22 ; Il - 23 Axis ; Osteogenesis
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 6
    Language: English
    In: Bone, December 2013, Vol.57(2), pp.484-492
    Description: Surgically induced periosteal membrane holds great potential for the treatment of large bone defects representing a simple alternative to combinations of exogenous stem cells, scaffolds and growth factors. The purpose of this study was to explore the biological basis for this novel regenerative medicine strategy in man. Eight patients with critical size defects were treated with the induced membrane (IM) technique. After membrane formation 1 cm biopsy was taken together with matched, healthy diaphyseal periosteum (P) for comparative analysis. Morphological characteristics, cell composition and growth factor expression were compared. Functional and molecular evaluation of mesenchymal stromal cell (MSC) activity was performed. Both tissues shared similar morphology although IM was significantly thicker than P (p = 0.032). The frequency of lymphocytes, pericytes (CD45 CD34 CD146 ) and cells expressing markers consistent with bone marrow MSCs (CD45 CD271 ) were 31. 3 and 15.5-fold higher respectively in IM (all p = 0.043). IM contained 3-fold more cells per gramme of tissue with a similar proportion of endothelial cells (CD45 CD31 ). Expressed bone morphogenic protein 2, vascular endothelial growth factor and stromal derived factor 1 (SDF-1) are key tissue regeneration mediators. Adherent expanded cells from both tissues had molecular profiles similar to bone marrow MSCs but cells from IM expressed greater than 2 fold relative abundance of SDF-1transcript compared to P (p = 0.043). The IM is a thick, vascularised structure that resembles periosteum with a cellular composition and molecular profile facilitating large defect repair and therefore may be described as an “induced-periosteum”. This tissue offers a powerful example of in situ tissue engineering.
    Keywords: Induced-Periosteum ; Induced Membrane ; Bone Regeneration ; Osteoprogenitor Cells ; Msc ; Medicine ; Anatomy & Physiology
    ISSN: 8756-3282
    E-ISSN: 1873-2763
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  • 7
    Language: English
    In: Regenerative Medicine, Sept, 2013, Vol.8(5), p.569(13)
    Description: Aim: To enumerate and characterize mesenchymal stem cells (MSCs) and endothelial cells (ECs) in umbilical cord (UC) tissue digests. Materials methods: Cultured UC cells were characterized phenotypically, and functionally by using 48-gene arrays. Native MSCs and ECs were enumerated using flow cytometry. Results: Compared with bone marrow (BM) MSCs, UC MSCs displayed significantly lower (range 4-240-fold) basal levels of bone-related transcripts, but their phenotypes were similar (CD73.sup.+ , CD105.sup.+ , CD90.sup.+ , CD45.sup.- and CD31.sup.- ). UC MSCs responded well to osteogenic induction, but day 21 postinduction levels remained below those achieved by BM MSCs. The total yield of native UC MSCs (CD90.sup.+ , CD45.sup.- and CD235[alpha].sup.- ) and ECs (CD31.sup.+ , CD45.sup.- and CD235[alpha].sup.- ) exceeded 150 and 15 million cells/donation, respectively. Both UC MSCs and ECs expressed CD146. Conclusion: While BM MSCs are more predisposed to osteogenesis, UC tissue harbors large numbers of MSCs and ECs; such minimally manipulated 'off-the-shelf' cellular mixtures can be used for regenerating bone in patients with compromised vascular supply.
    Keywords: Bone Regeneration -- Methods ; Stem Cells -- Identification And Classification ; Stem Cells -- Properties ; Umbilical Cord -- Genetic Aspects
    ISSN: 1746-0751
    Source: Cengage Learning, Inc.
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  • 8
    In: Stem Cells International, 2017, Vol.2017, 10 pages
    Description: . Culture expanded multipotential stromal cells (MSCs) have considerable potential for bone regeneration therapy but their wider use is constrained by the lack of simple and predictive assays of functional potency. Extended passaging leads to loss of multipotency but speed of decline depends on MSC donor age. The aim of this study was to develop an assay predictive of MSC culture longevity applicable to a broad donor age range.. Bone marrow (BM, ) was obtained from a diverse range (2–72 years) of healthy donors. MSCs were culture expanded to senescence and their osteoprogenitor content, gene expression profiles, epigenetic signature, and telomere behaviour were measured throughout. Output data was combined for modelling purposes.. Regardless of donor age, cultures’ osteoprogenitor content correlated better with remaining lifespan (population doublings before senescence, PD-BS) than proliferative history (accrued PDs). Individual gene’s expression or telomere length did not predict PD-BS but methylation of individual CpG islands did, PRAMEF2 in particular (). Coupling the steep relationship of relative expression with PD-BS () the formula × 1/PREMEF2 gave an improved correlation ().. A formula based onmRNA and PRAMEF2 methylation may be used to predict remaining BM-MSC longevity and related loss of multipotentiality independent of donor age.
    Keywords: Research Article;
    ISSN: 1687-966X
    E-ISSN: 1687-9678
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  • 9
    Language: English
    In: F1000Research, 6/11/2014
    ISSN: F1000Research
    E-ISSN: 2046-1402
    Source: CrossRef
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  • 10
    Language: English
    In: F1000Research, 2014, Vol.3, pp.126
    Description: Adult stem cells are characterised by longer telomeres compared to mature cells from the same tissue. In this study, candidate CD146 (+) umbilical cord (UC) mesenchymal stem cells (MSCs) were purified by cell sorting from UC tissue digests and their telomere lengths were measured in comparison to donor-matched CD146-negative fraction. UC tissue fragments were enzymatically treated with collagenase and the cells were used for cell sorting, colony-forming fibroblast (CFU-F) assay or for long-term MSC cultivation. Telomere lengths were measured by qPCR in both culture-expanded MSCs and candidate native UC MSCs. Immunohistochemistry was undertaken to study the topography of CD146 (+) cells. Culture-expanded UC MSCs had a stable expression of CD73, CD90 and CD105, whereas CD146 declined in later passages which correlated with the shortening of telomeres in the same cultures. In three out of four donors, telomeres in candidate native UC MSCs (CD45 (-)CD235α (-)CD31 (-)CD146 (+)) were longer compared to donor-matched CD146 (-) population (CD45 (-)CD235α (-)CD31 (-)CD146 (-)). The frequency of CD45 (-)CD235α (-)CD31 (-)CD146 (+) cells measured by flow cytometry was ~1000-fold above that of donor-matched CFU-Fs (means 10.4% and 0.01%, respectively). CD146 (+) cells were also abundant in situ having a broad topography including high levels of positivity in muscle areas in addition to vessels.
    Keywords: Medicine ; Women'S Studies;
    ISSN: 2046-1402
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