دورية أكاديمية
Mesenchymal stromal cell-secreted chemerin is a novel immunomodulatory molecule driving the migration of ChemR23-expressing cells.
العنوان: | Mesenchymal stromal cell-secreted chemerin is a novel immunomodulatory molecule driving the migration of ChemR23-expressing cells. |
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المؤلفون: | Vinci P; Centro di Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy., Bastone A; Istituto di ricovero e cura a carattere scientifico-Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy., Schiarea S; Istituto di ricovero e cura a carattere scientifico-Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy., Cappuzzello C; Centro di Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy., Del Prete A; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; Humanitas Clinical and Research Center, Rozzano, Italy., Dander E; Centro di Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy., Biondi A; Centro di Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy; Clinica Pediatrica, Università di Milano-Bicocca, Fondazione Monza e Brianza per il Bambino e la sua Mamma/Ospedale S. Gerardo, Monza, Italy., D'Amico G; Centro di Ricerca Tettamanti, Clinica Pediatrica, Università di Milano-Bicocca, Monza, Italy. Electronic address: giovanna.damico@hsgerardo.org. |
المصدر: | Cytotherapy [Cytotherapy] 2017 Feb; Vol. 19 (2), pp. 200-210. Date of Electronic Publication: 2016 Dec 06. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Country of Publication: England NLM ID: 100895309 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-2566 (Electronic) Linking ISSN: 14653249 NLM ISO Abbreviation: Cytotherapy Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2013- : London : Elsevier Original Publication: Oxford, England : ISIS Medical Media, c1999- |
مواضيع طبية MeSH: | Chemotaxis/*drug effects , Chimerin Proteins/*pharmacology , Immunomodulation/*drug effects , Mesenchymal Stem Cells/*metabolism , Receptors, Chemokine/*metabolism, Blood Platelets/chemistry ; Cell Culture Techniques ; Cell Extracts/chemistry ; Cell Extracts/pharmacology ; Cells, Cultured ; Chemotaxis/genetics ; Chimerin Proteins/genetics ; Chimerin Proteins/metabolism ; Culture Media/metabolism ; Culture Media/pharmacology ; Human Umbilical Vein Endothelial Cells ; Humans ; Immunomodulation/genetics ; Inflammation/metabolism ; Inflammation/therapy ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/cytology ; Receptors, Chemokine/genetics |
مستخلص: | Background: Mesenchymal stromal cells (MSCs) are multipotent cells characterized by broad immunomodulatory properties exploited for the treatment of inflammatory disorders. However, the efficacy of MSC-based therapy is highly variable and tightly linked to MSC culture conditions and treatment schedule. Thus, the identification of novel key molecules regulating MSC immunomodulatory activities in vivo might constitute a crucial step toward the optimization of currently available clinical protocols. In this regard, herein, we sought to determine whether the newly identified chemotactic protein, chemerin, plays a role in MSC-mediated regulation of inflammation. Methods: Chemerin production by human MSCs was investigated under different culture conditions using enzyme-linked immunosorbent assay (ELISA). After purification, MSC-secreted chemerin was identified using mass spectrometry analysis and the biological activity of secreted isoforms was evaluated using migration assay. Results: Bone marrow-derived MSCs secrete chemerin and express its receptors ChemR23 and CCRL2. Chemerin production is dependent on culture conditions and increases upon stimulation with inflammatory cytokines. In particular, platelet lysate (PL)-MSCs produce higher levels of chemerin compared with fetal bovine serum (FBS)-MSCs. Furthermore, chemerin is secreted by MSCs as an inactive precursor, which can be converted into its active form by exogenous chemerin-activating serine and cysteine proteases. Discussion: Our data indicate that, in response to various inflammatory stimuli, MSCs secrete high amounts of inactive chemerin, which can then be activated by inflammation-induced tissue proteases. In light of these initial findings, we propose that further analysis of chemerin functions in vivo might constitute a crucial step toward optimizing MSC-based therapy for inflammatory diseases. (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: ChemR23 receptor; chemerin; immunomodulation; mesenchymal stromal cells |
المشرفين على المادة: | 0 (CMKLR1 protein, human) 0 (Cell Extracts) 0 (Chimerin Proteins) 0 (Culture Media) 0 (Receptors, Chemokine) |
تواريخ الأحداث: | Date Created: 20161213 Date Completed: 20170802 Latest Revision: 20181202 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.jcyt.2016.11.006 |
PMID: | 27939374 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1477-2566 |
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DOI: | 10.1016/j.jcyt.2016.11.006 |