دورية أكاديمية
Mesenchymal Stromal Cell Derived Membrane Particles Are Internalized by Macrophages and Endothelial Cells Through Receptor-Mediated Endocytosis and Phagocytosis.
| العنوان: | Mesenchymal Stromal Cell Derived Membrane Particles Are Internalized by Macrophages and Endothelial Cells Through Receptor-Mediated Endocytosis and Phagocytosis. |
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| المؤلفون: | da Costa Gonçalves F; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands., Korevaar SS; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands., Ortiz Virumbrales M; Takeda Madrid, Cell Therapy Technology Center, Madrid, Spain., Baan CC; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands., Reinders MEJ; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands., Merino A; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands., Lombardo E; Takeda Madrid, Cell Therapy Technology Center, Madrid, Spain., Hoogduijn MJ; Nephrology and Transplantation, Internal Medicine, Erasmus Medical Center Transplantation Institute, Erasmus Medical Center, Rotterdam, Netherlands. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Mar 15; Vol. 12, pp. 651109. Date of Electronic Publication: 2021 Mar 15 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Cell- and Tissue-Based Therapy/*methods , Cell-Derived Microparticles/*immunology , Mesenchymal Stem Cells/*cytology, Cell-Derived Microparticles/transplantation ; Cells, Cultured ; Dose-Response Relationship, Immunologic ; Healthy Volunteers ; Human Umbilical Vein Endothelial Cells ; Humans ; Macrophages/immunology ; Mesenchymal Stem Cells/immunology ; Phagocytosis/immunology ; Pinocytosis/immunology ; Primary Cell Culture ; Subcutaneous Fat/cytology |
| مستخلص: | Mesenchymal stromal cells (MSC) are a promising therapy for inflammatory diseases. However, MSC are large and become trapped in the lungs after intravenous infusion, where they have a short survival time. To steer MSC immunoregulatory therapy beyond the lungs, we generated nm-sized particles from MSC membranes (membrane particles, MP), which have immunomodulatory properties, and investigated their internalization and mode of interaction in macrophages subtypes and human umbilical vein endothelial cells (HUVEC) under control and inflammatory conditions. We found that macrophages and HUVEC take up MP in a dose, time, and temperature-dependent manner. Specific inhibitors for endocytotic pathways revealed that MP internalization depends on heparan sulfate proteoglycan-, dynamin-, and clathrin-mediated endocytosis but does not involve caveolin-mediated endocytosis. MP uptake also involved the actin cytoskeleton and phosphoinositide 3-kinase, which are implicated in macropinocytosis and phagocytosis. Anti-inflammatory M2 macrophages take up more MP than pro-inflammatory M1 macrophages. In contrast, inflammatory conditions did not affect the MP uptake by HUVEC. Moreover, MP induced both anti- and pro-inflammatory responses in macrophages and HUVEC by affecting gene expression and cell surface proteins. Our findings on the mechanisms of uptake of MP under different conditions help the development of target-cell specific MP therapy to modulate immune responses. Competing Interests: MO and EL were employed by Takeda Madrid. Erasmus MC filed a patent on MSC derived MP (PCT/NL2017/050334). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 da Costa Gonçalves, Korevaar, Ortiz Virumbrales, Baan, Reinders, Merino, Lombardo and Hoogduijn.) |
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| فهرسة مساهمة: | Keywords: endocytosis; endothelial cells; extracellular vesicles; immunomodulation; macrophages; membrane particles; mesenchymal stromal cells; phagocytosis |
| تواريخ الأحداث: | Date Created: 20210401 Date Completed: 20210924 Latest Revision: 20210924 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8005704 |
| DOI: | 10.3389/fimmu.2021.651109 |
| PMID: | 33790914 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.651109 |