title: Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells.
abstract: Mesenchymal stromal cells (MSCs) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 h to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 h post irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow. The murine hematopoietic cell line, FDC-P1 exposed to 500cGy, showed reversal of growth inhibition, DNA damage and apoptosis on exposure to murine or human MSC-EVs. Both murine and human MSC-EVs reverse radiation damage to murine marrow cells and stimulate normal murine marrow stem cell/progenitors to proliferate. A preparation with both exosomes and microvesicles was found to be superior to either microvesicles or exosomes alone. Biologic activity was seen in freshly isolated vesicles and in vesicles stored for up to 6 months in 10% dimethyl sulfoxide at -80 °C. These studies indicate that MSC-EVs can reverse radiation damage to bone marrow stem cells.
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wen
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Dooner
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: E
authors.initials: E
authors.lastname: Papa
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Del Tatto
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pereira
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: L
authors.initials: L
authors.lastname: Goldberg
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: J
authors.initials: J
authors.lastname: Aliotta
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: C
authors.initials: C
authors.lastname: Stewart
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carpanetto
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Collino
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bruno
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.affiliation: Division of Hematology/Oncology, Brown University, Rhode Island Hospital, Providence, RI, USA.
authors.forename: P
authors.initials: P
authors.lastname: Quesenberry
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D004249:DNA Damage; D000067128:Extracellular Vesicles / Q000502:physiology* / Q000637:transplantation; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D011830:Radiation Effects; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous; D016896:Treatment Outcome