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...

Full description

Bibliographic Details
Main Authors: Maximilian Haertinger, Tamara Weiss, Anda Mann, Annette Tabi, Victoria Brandel, Christine Radtke
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/1/163
_version_ 1827853231775023104
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.
first_indexed 2024-03-12T11:03:14Z
format Article
id doaj.art-31abf558c5e74825b4963389b2af6741
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-03-12T11:03:14Z
publishDate 2020-01-01
publisher MDPI AG
record_format Article
series Cells
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
work_keys_str_mv AT maximilianhaertinger adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization
AT tamaraweiss adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization
AT andamann adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization
AT annettetabi adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization
AT victoriabrandel adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization
AT christineradtke adiposestemcellderivedextracellularvesiclesinduceproliferationofschwanncellsviainternalization