We are analyzing https://link.springer.com/article/10.1186/1741-7015-11-146.

Title:
Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells | BMC Medicine
Description:
Background Mesenchymal 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. Methods BM-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. Results BM-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. Conclusions By 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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Keywords {🔍}

cells, cell, bmmsc, pubmed, bmmscs, stem, preparations, article, donors, expression, google, scholar, mesenchymal, figure, differentiation, mrna, cas, human, age, potential, correlation, female, donor, msc, proliferation, mscs, male, markers, detected, analysis, prdm, compared, vitro, bone, stromal, growth, subpopulations, gender, correlated, specific, ido, factors, oct, file, nanog, data, adipogenic, twotailed, marrow, functional,

Topics {✒️}

open access article acute graft-versus-host disease bm-msc-derived trophic factors apheresis-derived platelet concentrates open-label pre-test graft-versus-host disease age-related post-transcriptional impact mouse bone marrow human bone marrow octamer-binding transcription factor adult bone marrow paracrine soluble factors stage-specific embryonic antigen bm-msc-secreted trophic factors mesenchymal stromal cells adult human bm-mscs pre-publication history cd10-cd119-gd2+ bm-msc subpopulations rnase-free dnase set wnt5/calmodulin signalling pathway dextro-1-methyl tryptophan abrogates bm-msc subpopulations expressing bm-msc-mediated immunomodulation human bm-msc preparations cell numberharvested/cell numberseeded cell clones derived related subjects high-clonogenic bm-msc subpopulation tissue repair–current views multipotential stromal cells human bm-msc function pre-bii cell development mediate therapeutic potential fewer bm-msc preparations stage-specific embryonic antigens mesodermal progenitor cells full size image full access mesenchymal stem cells mediate tissue regeneration article download pdf pluripotent human escs representative bm-msc preparation sorted bm-msc subpopulations anti-brdu antibody provided pooled human serum prominent inter-individual heterogeneity respective bm-msc preparations richard schäfer cell-based therapies ranging

Questions {❓}

Schäfer R: Does the adult stroma contain stem cells?

Schema {🗺️}

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         description:Mesenchymal 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. BM-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. BM-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. By 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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      name:Department of Orthopaedic Surgery, University Hospital Tübingen, Tübingen, Germany
      name:Institute of Clinical and Experimental Transfusion Medicine (IKET), University Hospital Tübingen, Tübingen, Germany
      name:German Red Cross Blood Service of Baden-Württemberg-Hessen, Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, Heidelberg University, Mannheim, Germany
      name:Institute of Clinical and Experimental Transfusion Medicine (IKET), University Hospital Tübingen, Tübingen, Germany
      name:Institute of Clinical and Experimental Transfusion Medicine (IKET), University Hospital Tübingen, Tübingen, Germany
      name:Department of Neurosurgery, Stanford Institute for Neuro-Innovation and Translational Neurosciences, Stanford University School of Medicine, Stanford, USA

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