Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model
We have previously shown that injury induced by irradiation to murine marrow can be partially or completely reversed by exposure to human or murine mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Investigation of the biodistribution of EVs in vivo is essential for understanding EV...
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doaj-25eb97977e2d4845adf2ef3a45fa37e92020-11-25T01:42:14ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-11-012021546810.3390/ijms20215468ijms20215468Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine ModelSicheng Wen0Mark Dooner1Elaine Papa2Michael Del Tatto3Mandy Pereira4Theodor Borgovan5Yan Cheng6Laura Goldberg7Olin Liang8Giovanni Camussi9Peter Quesenberry10Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USADepartment of Medical Sciences, University of Torino, 10126 Torino, ItalyDivision of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI 02903, USAWe have previously shown that injury induced by irradiation to murine marrow can be partially or completely reversed by exposure to human or murine mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Investigation of the biodistribution of EVs in vivo is essential for understanding EV biology. In this study, we evaluated the DiD lipid dye labeled MSC-EV biodistribution in mice under different conditions, including different MSC-EV doses and injection schedules, time post MSC-EV injection, and doses of radiation. DiD-labeled MSC-EVs appeared highest in the liver and spleen; lower in bone marrow of the tibia, femur, and spine; and were undetectable in the heart, kidney and lung, while a predominant EV accumulation was detected in the lung of mice infused with human lung fibroblast cell derived EVs. There was significantly increased MSC-EV accumulation in the spleen and bone marrow (tibia and femur) post radiation appearing with an increase of MSC-EV uptake by CD11b+ and F4/80+ cells, but not by B220 cells, compared to those organs from non-irradiated mice. We further demonstrated that increasing levels of irradiation caused a selective increase in vesicle homing to marrow. This accumulation of MSC-EVs at the site of injured bone marrow could be detected as early as 1 h after MSC- EV injection and was not significantly different between 2 and 24 h post MSC-EV injection. Our study indicates that irradiation damage to hematopoietic tissue in the spleen and marrow targets MSC-EVs to these tissues.https://www.mdpi.com/1422-0067/20/21/5468biodistributionextracellular vesicleradiation injurymesenchymal stem cell |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sicheng Wen Mark Dooner Elaine Papa Michael Del Tatto Mandy Pereira Theodor Borgovan Yan Cheng Laura Goldberg Olin Liang Giovanni Camussi Peter Quesenberry |
spellingShingle |
Sicheng Wen Mark Dooner Elaine Papa Michael Del Tatto Mandy Pereira Theodor Borgovan Yan Cheng Laura Goldberg Olin Liang Giovanni Camussi Peter Quesenberry Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model International Journal of Molecular Sciences biodistribution extracellular vesicle radiation injury mesenchymal stem cell |
author_facet |
Sicheng Wen Mark Dooner Elaine Papa Michael Del Tatto Mandy Pereira Theodor Borgovan Yan Cheng Laura Goldberg Olin Liang Giovanni Camussi Peter Quesenberry |
author_sort |
Sicheng Wen |
title |
Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model |
title_short |
Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model |
title_full |
Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model |
title_fullStr |
Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model |
title_full_unstemmed |
Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model |
title_sort |
biodistribution of mesenchymal stem cell-derived extracellular vesicles in a radiation injury bone marrow murine model |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-11-01 |
description |
We have previously shown that injury induced by irradiation to murine marrow can be partially or completely reversed by exposure to human or murine mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Investigation of the biodistribution of EVs in vivo is essential for understanding EV biology. In this study, we evaluated the DiD lipid dye labeled MSC-EV biodistribution in mice under different conditions, including different MSC-EV doses and injection schedules, time post MSC-EV injection, and doses of radiation. DiD-labeled MSC-EVs appeared highest in the liver and spleen; lower in bone marrow of the tibia, femur, and spine; and were undetectable in the heart, kidney and lung, while a predominant EV accumulation was detected in the lung of mice infused with human lung fibroblast cell derived EVs. There was significantly increased MSC-EV accumulation in the spleen and bone marrow (tibia and femur) post radiation appearing with an increase of MSC-EV uptake by CD11b+ and F4/80+ cells, but not by B220 cells, compared to those organs from non-irradiated mice. We further demonstrated that increasing levels of irradiation caused a selective increase in vesicle homing to marrow. This accumulation of MSC-EVs at the site of injured bone marrow could be detected as early as 1 h after MSC- EV injection and was not significantly different between 2 and 24 h post MSC-EV injection. Our study indicates that irradiation damage to hematopoietic tissue in the spleen and marrow targets MSC-EVs to these tissues. |
topic |
biodistribution extracellular vesicle radiation injury mesenchymal stem cell |
url |
https://www.mdpi.com/1422-0067/20/21/5468 |
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