title: Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells.
abstract: BACKGROUND
  Malignant glial tumors, including glioblastoma multiforme, account for 15 - 20% of pediatric CNS malignancies. They are most resistant to therapy and are associated with a poor prognosis.
  
  
  OBJECTIVE
  Given the ability of mesenchymal stem cells (MSCs) to affect glioma growth, we investigated the effects of extracellular vesicles (EVs) derived from MSCs on U87MG glioblastoma cells line.
  
  
  METHODS
  EVs were isolated from culture media of MSCs from different sources, including bone marrow (BM), umbilical cord (UC) and adipose tissue (AT) and added to U87MG culture. The internalization and the effects of BM-, UC- and AT-MSC-EVs on proliferation and apoptosis of tumor cells were evaluated.
  
  
  RESULTS
  Both confocal microscopy and FACS analysis showed internalization of EVs into tumor cells. BM- and UC-MSC-EVs decreased cell proliferation, while an opposite effect was observed with AT-MSC-EVs. Moreover, both BM- and UC-MSC-EVs induced apoptosis of glioblastoma cells, while AT-MSC-EVs had no effect. Loading UC-MSC-EVs with Vincristine further increased cytotoxicity when compared both to the free drug and to untreated EVs.
  
  
  CONCLUSIONS
  Different effects of MSC-EVs on cancer cells were observed depending on their tissue of origin. Moreover, MSC-EVs can deliver antiblastic drugs to glioblastoma cells.
authors.affiliation: Bambino Gesù Children's Hospital, Regenerative Medicine Unit, IRCCS , Piazza Sant'Onofrio 4, Rome 00165 , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Del Fattore
authors.forename: Rosa
authors.initials: R
authors.lastname: Luciano
authors.forename: Rossana
authors.initials: R
authors.lastname: Saracino
authors.forename: Giulia
authors.initials: G
authors.lastname: Battafarano
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rizzo
authors.forename: Luisa
authors.initials: L
authors.lastname: Pascucci
authors.forename: Giulio
authors.initials: G
authors.lastname: Alessandri
authors.forename: Augusto
authors.initials: A
authors.lastname: Pessina
authors.forename: Antonio
authors.initials: A
authors.lastname: Perrotta
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fierabracci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muraca
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology* / Q000628:therapy; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism*; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine
keywords: Vincristine; extracellular vesicles; glioblastoma; mesenchymal stem/stromal cells