Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization
Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor bi...
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MDPI AG
2020-01-01
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author | Maximilian Haertinger Tamara Weiss Anda Mann Annette Tabi Victoria Brandel Christine Radtke |
author_facet | Maximilian Haertinger Tamara Weiss Anda Mann Annette Tabi Victoria Brandel Christine Radtke |
author_sort | Maximilian Haertinger |
collection | DOAJ |
description | Recent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration. |
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last_indexed | 2024-03-12T11:03:14Z |
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spelling | doaj.art-31abf558c5e74825b4963389b2af67412023-09-02T04:30:14ZengMDPI AGCells2073-44092020-01-019116310.3390/cells9010163cells9010163Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via InternalizationMaximilian Haertinger0Tamara Weiss1Anda Mann2Annette Tabi3Victoria Brandel4Christine Radtke5Research Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaResearch Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaResearch Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaResearch Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaResearch Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaResearch Laboratory of the Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaRecent studies showed a beneficial effect of adipose stem cell-derived extracellular vesicles (ADSC-EVs) on sciatic nerve repair, presumably through Schwann cell (SC) modulation. However, it has not yet been elucidated whether ADSC-EVs exert this supportive effect on SCs by extracellular receptor binding, fusion to the SC membrane, or endocytosis mediated internalization. ADSCs, ADSC-EVs, and SCs were isolated from rats and characterized according to associated marker expression and properties. The proliferation rate of SCs in response to ADSC-EVs was determined using a multicolor immunofluorescence staining panel followed by automated image analysis. SCs treated with ADSC-EVs and silica beads were further investigated by 3-D high resolution confocal microscopy and live cell imaging. Our findings demonstrated that ADSC-EVs significantly enhanced the proliferation of SCs in a time- and dose-dependent manner. 3-D image analysis revealed a perinuclear location of ADSC-EVs and their accumulation in vesicular-like structures within the SC cytoplasm. Upon comparing intracellular localization patterns of silica beads and ADSC-EVs in SCs, we found striking resemblance in size and distribution. Live cell imaging visualized that the uptake of ADSC-EVs preferentially took place at the SC processes from which the EVs were transported towards the nucleus. This study provided first evidence for an endocytosis mediated internalization of ADSC-EVs by SCs and underlines the therapeutic potential of ADSC-EVs in future approaches for nerve regeneration.https://www.mdpi.com/2073-4409/9/1/163schwann cellsadipose-derived stem cellsextracellular vesiclesendocytosisproliferationnerve regenerationnerve injury |
spellingShingle | Maximilian Haertinger Tamara Weiss Anda Mann Annette Tabi Victoria Brandel Christine Radtke Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization Cells schwann cells adipose-derived stem cells extracellular vesicles endocytosis proliferation nerve regeneration nerve injury |
title | Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization |
title_full | Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization |
title_fullStr | Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization |
title_full_unstemmed | Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization |
title_short | Adipose Stem Cell-Derived Extracellular Vesicles Induce Proliferation of Schwann Cells via Internalization |
title_sort | adipose stem cell derived extracellular vesicles induce proliferation of schwann cells via internalization |
topic | schwann cells adipose-derived stem cells extracellular vesicles endocytosis proliferation nerve regeneration nerve injury |
url | https://www.mdpi.com/2073-4409/9/1/163 |
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