title: Rat multipotent mesenchymal stromal cells lack long-distance tropism to 3 different rat glioma models.
abstract: BACKGROUND
  Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy.
  
  
  OBJECTIVE
  To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models.
  
  
  METHODS
  Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas.
  
  
  RESULTS
  We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection.
  
  
  CONCLUSIONS
  The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.
authors.affiliation: Lund Stem Cell Center, Lund University, Lund, Sweden. daniel.bexell@med.lu.se
authors.forename: Daniel
authors.initials: D
authors.lastname: Bexell
authors.forename: Salina
authors.initials: S
authors.lastname: Gunnarsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Svensson
authors.forename: Ariane
authors.initials: A
authors.lastname: Tormin
authors.forename: Catarina
authors.initials: C
authors.lastname: Henriques-Oliveira
authors.forename: Peter
authors.initials: P
authors.lastname: Siesjö
authors.forename: Gesine
authors.initials: G
authors.lastname: Paul
authors.forename: Leif G
authors.initials: LG
authors.lastname: Salford
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
authors.forename: Johan
authors.initials: J
authors.lastname: Bengzon
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003337:Corpus Callosum / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D049452:Green Fluorescent Proteins